Hypopituitarism medical therapy: Difference between revisions

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__NOTOC__
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{{Hypopituitarism }}
{{Hypopituitarism }}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{IQ}}


==Overview==
==Overview==
*The mainstay of treatment for [disease name] is [therapy].
The mainstay of treatment for hypopituitarism is [[hormone replacement therapy]] and treating the underlying cause. [[Adrenocorticotropic hormone|Adrenocorticotrophic hormone]] ([[Adrenocorticotropic hormone|ACTH]]) deficiency is treated with [[glucocorticoids]]. [[Gonadotropin deficiency]] is treated with [[testosterone]] in men and [[estrogen]] with or without [[progesterone]] in women. [[Hypothyroidism]] is treated with [[levothyroxine]]. [[Growth hormone]] (GH) is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other [[pituitary]] hormones.
 


==Medical Therapy==
==Medical Therapy==
*Treatment involves appropriate [[hormone replacement therapy]], which must be taken for the rest of your life that results in significant improvement and reversal of not only the physical symptoms, but also the [[psychological]] symptoms.<ref name="pmid27034575">{{cite journal |vauthors=Parikh R, Buch V, Makwana M, Buch HN |title=The price of a 15-year delay in diagnosis of Sheehan's syndrome |journal=Proc (Bayl Univ Med Cent) |volume=29 |issue=2 |pages=212–3 |year=2016 |pmid=27034575 |pmc=4790577 |doi= |url=}}</ref><ref name="pmid19697029">{{cite journal |vauthors=Laway BA, Bhat JR, Mir SA, Khan RS, Lone MI, Zargar AH |title=Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review) |journal=Ann. Hematol. |volume=89 |issue=3 |pages=305–8 |year=2010 |pmid=19697029 |doi=10.1007/s00277-009-0804-9 |url=}}</ref><ref name="pmid15921942">{{cite journal |vauthors=Tanriverdi F, Unluhizarci K, Kula M, Guven M, Bayram F, Kelestimur F |title=Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome |journal=Growth Horm. IGF Res. |volume=15 |issue=3 |pages=231–7 |year=2005 |pmid=15921942 |doi=10.1016/j.ghir.2005.03.005 |url=}}</ref><ref name="pmid9059561">{{cite journal |vauthors=Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM |title=Increased cerebrovascular mortality in patients with hypopituitarism |journal=Clin. Endocrinol. (Oxf) |volume=46 |issue=1 |pages=75–81 |year=1997 |pmid=9059561 |doi= |url=}}</ref><ref name="pmid12675508">{{cite journal |vauthors=Arafah BM |title=Medical management of hypopituitarism in patients with pituitary adenomas |journal=Pituitary |volume=5 |issue=2 |pages=109–17 |year=2002 |pmid=12675508 |doi= |url=}}</ref><ref name="pmid20719838">{{cite journal |vauthors=Grossman AB |title=Clinical Review#: The diagnosis and management of central hypoadrenalism |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=11 |pages=4855–63 |year=2010 |pmid=20719838 |doi=10.1210/jc.2010-0982 |url=}}</ref><ref name="pmid1986026">{{cite journal |vauthors=Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL |title=Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry |journal=J. Clin. Endocrinol. Metab. |volume=72 |issue=1 |pages=39–45 |year=1991 |pmid=1986026 |doi=10.1210/jcem-72-1-39 |url=}}</ref><ref name="pmid16584509">{{cite journal |vauthors=Arlt W, Rosenthal C, Hahner S, Allolio B |title=Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements |journal=Clin. Endocrinol. (Oxf) |volume=64 |issue=4 |pages=384–9 |year=2006 |pmid=16584509 |doi=10.1111/j.1365-2265.2006.02473.x |url=}}</ref><ref name="pmid17437510">{{cite journal |vauthors=Thomson AH, Devers MC, Wallace AM, Grant D, Campbell K, Freel M, Connell JM |title=Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency |journal=Clin. Endocrinol. (Oxf) |volume=66 |issue=6 |pages=789–96 |year=2007 |pmid=17437510 |doi=10.1111/j.1365-2265.2007.02812.x |url=}}</ref><ref name="pmid4182323">{{cite journal |vauthors=Martin MM |title=Coexisting anterior pituitary and neurohypophyseal insufficiency. A syndrome with diagnostic implication |journal=Arch. Intern. Med. |volume=123 |issue=4 |pages=409–16 |year=1969 |pmid=4182323 |doi= |url=}}</ref><ref name="pmid2019265">{{cite journal |vauthors=Shibata H, Ogishima T, Mitani F, Suzuki H, Murakami M, Saruta T, Ishimura Y |title=Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium |journal=Endocrinology |volume=128 |issue=5 |pages=2534–9 |year=1991 |pmid=2019265 |doi=10.1210/endo-128-5-2534 |url=}}</ref><ref name="pmid8015573">{{cite journal |vauthors=White PC |title=Disorders of aldosterone biosynthesis and action |journal=N. Engl. J. Med. |volume=331 |issue=4 |pages=250–8 |year=1994 |pmid=8015573 |doi=10.1056/NEJM199407283310408 |url=}}</ref><ref name="pmid11158009">{{cite journal |vauthors=Miller KK, Sesmilo G, Schiller A, Schoenfeld D, Burton S, Klibanski A |title=Androgen deficiency in women with hypopituitarism |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=2 |pages=561–7 |year=2001 |pmid=11158009 |doi=10.1210/jcem.86.2.7246 |url=}}</ref><ref name="pmid16478814">{{cite journal |vauthors=Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A |title=Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study |journal=J. Clin. Endocrinol. Metab. |volume=91 |issue=5 |pages=1683–90 |year=2006 |pmid=16478814 |doi=10.1210/jc.2005-2596 |url=}}</ref>
*Treatment involves appropriate [[hormone replacement therapy]], which must be taken for the rest of your life that results in significant improvement and reversal of not only the physical symptoms, but also the [[psychological]] symptoms.<ref name="pmid27034575">{{cite journal |vauthors=Parikh R, Buch V, Makwana M, Buch HN |title=The price of a 15-year delay in diagnosis of Sheehan's syndrome |journal=Proc (Bayl Univ Med Cent) |volume=29 |issue=2 |pages=212–3 |year=2016 |pmid=27034575 |pmc=4790577 |doi= |url=}}</ref><ref name="pmid19697029">{{cite journal |vauthors=Laway BA, Bhat JR, Mir SA, Khan RS, Lone MI, Zargar AH |title=Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review) |journal=Ann. Hematol. |volume=89 |issue=3 |pages=305–8 |year=2010 |pmid=19697029 |doi=10.1007/s00277-009-0804-9 |url=}}</ref><ref name="pmid15921942">{{cite journal |vauthors=Tanriverdi F, Unluhizarci K, Kula M, Guven M, Bayram F, Kelestimur F |title=Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome |journal=Growth Horm. IGF Res. |volume=15 |issue=3 |pages=231–7 |year=2005 |pmid=15921942 |doi=10.1016/j.ghir.2005.03.005 |url=}}</ref><ref name="pmid9059561">{{cite journal |vauthors=Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM |title=Increased cerebrovascular mortality in patients with hypopituitarism |journal=Clin. Endocrinol. (Oxf) |volume=46 |issue=1 |pages=75–81 |year=1997 |pmid=9059561 |doi= |url=}}</ref><ref name="pmid12675508">{{cite journal |vauthors=Arafah BM |title=Medical management of hypopituitarism in patients with pituitary adenomas |journal=Pituitary |volume=5 |issue=2 |pages=109–17 |year=2002 |pmid=12675508 |doi= |url=}}</ref><ref name="pmid20719838">{{cite journal |vauthors=Grossman AB |title=Clinical Review#: The diagnosis and management of central hypoadrenalism |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=11 |pages=4855–63 |year=2010 |pmid=20719838 |doi=10.1210/jc.2010-0982 |url=}}</ref><ref name="pmid1986026">{{cite journal |vauthors=Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL |title=Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry |journal=J. Clin. Endocrinol. Metab. |volume=72 |issue=1 |pages=39–45 |year=1991 |pmid=1986026 |doi=10.1210/jcem-72-1-39 |url=}}</ref><ref name="pmid16584509">{{cite journal |vauthors=Arlt W, Rosenthal C, Hahner S, Allolio B |title=Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements |journal=Clin. Endocrinol. (Oxf) |volume=64 |issue=4 |pages=384–9 |year=2006 |pmid=16584509 |doi=10.1111/j.1365-2265.2006.02473.x |url=}}</ref><ref name="pmid17437510">{{cite journal |vauthors=Thomson AH, Devers MC, Wallace AM, Grant D, Campbell K, Freel M, Connell JM |title=Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency |journal=Clin. Endocrinol. (Oxf) |volume=66 |issue=6 |pages=789–96 |year=2007 |pmid=17437510 |doi=10.1111/j.1365-2265.2007.02812.x |url=}}</ref><ref name="pmid4182323">{{cite journal |vauthors=Martin MM |title=Coexisting anterior pituitary and neurohypophyseal insufficiency. A syndrome with diagnostic implication |journal=Arch. Intern. Med. |volume=123 |issue=4 |pages=409–16 |year=1969 |pmid=4182323 |doi= |url=}}</ref><ref name="pmid2019265">{{cite journal |vauthors=Shibata H, Ogishima T, Mitani F, Suzuki H, Murakami M, Saruta T, Ishimura Y |title=Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium |journal=Endocrinology |volume=128 |issue=5 |pages=2534–9 |year=1991 |pmid=2019265 |doi=10.1210/endo-128-5-2534 |url=}}</ref><ref name="pmid8015573">{{cite journal |vauthors=White PC |title=Disorders of aldosterone biosynthesis and action |journal=N. Engl. J. Med. |volume=331 |issue=4 |pages=250–8 |year=1994 |pmid=8015573 |doi=10.1056/NEJM199407283310408 |url=}}</ref><ref name="pmid11158009">{{cite journal |vauthors=Miller KK, Sesmilo G, Schiller A, Schoenfeld D, Burton S, Klibanski A |title=Androgen deficiency in women with hypopituitarism |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=2 |pages=561–7 |year=2001 |pmid=11158009 |doi=10.1210/jcem.86.2.7246 |url=}}</ref><ref name="pmid16478814">{{cite journal |vauthors=Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A |title=Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study |journal=J. Clin. Endocrinol. Metab. |volume=91 |issue=5 |pages=1683–90 |year=2006 |pmid=16478814 |doi=10.1210/jc.2005-2596 |url=}}</ref>
*Management usually involves orally-administered target organ [[hormone]] replacement except for [[growth hormone]] ([[GH]]) and [[antidiuretic hormone]] ([[Antidiuretic hormone|ADH]])
=== 1.ACTH deficiency ===
<ref name="pmid9156031">{{cite journal |vauthors=Peacey SR, Guo CY, Robinson AM, Price A, Giles MA, Eastell R, Weetman AP |title=Glucocorticoid replacement therapy: are patients over treated and does it matter? |journal=Clin. Endocrinol. (Oxf) |volume=46 |issue=3 |pages=255–61 |year=1997 |pmid=9156031 |doi= |url=}}</ref><ref name="pmid12788587">{{cite journal |vauthors=Arlt W, Allolio B |title=Adrenal insufficiency |journal=Lancet |volume=361 |issue=9372 |pages=1881–93 |year=2003 |pmid=12788587 |doi=10.1016/S0140-6736(03)13492-7 |url=}}</ref><ref name="pmid9156032">{{cite journal |vauthors=Howlett TA |title=An assessment of optimal hydrocortisone replacement therapy |journal=Clin. Endocrinol. (Oxf) |volume=46 |issue=3 |pages=263–8 |year=1997 |pmid=9156032 |doi= |url=}}</ref><ref name="pmid1986026">{{cite journal |vauthors=Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL |title=Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry |journal=J. Clin. Endocrinol. Metab. |volume=72 |issue=1 |pages=39–45 |year=1991 |pmid=1986026 |doi=10.1210/jcem-72-1-39 |url=}}</ref><ref name="pmid3256">{{cite journal |vauthors=Besser GM, Jeffcoate WJ |title=Endocrine and metabolic diseases. Adrenal diseases |journal=Br Med J |volume=1 |issue=6007 |pages=448–51 |year=1976 |pmid=3256 |pmc=1638946 |doi= |url=}}</ref><ref name="pmid8321791">{{cite journal |vauthors=Peacey SR, Pope RM, Naik KS, Hardern RD, Page MD, Belchetz PE |title=Corticosteroid therapy and intercurrent illness: the need for continuing patient education |journal=Postgrad Med J |volume=69 |issue=810 |pages=282–4 |year=1993 |pmid=8321791 |pmc=2399661 |doi= |url=}}</ref>


=== '''ACTH deficiency''' ===
==== 1.1.Acute setting ====
* Preferred regimen: [[Hydrocortisone]] 100 mg [[Intravenous|IV]] [[Bolus (medicine)|bolus]], then 300 mg/day [[Intravenous|IV]] divided q8hr '''or''' continuous [[infusion]] for 48 hours
** Once patient is stable: 50 mg [[Oral|PO]] q8hr for 6 doses, later on tapered to 30-50 mg/day [[Oral|PO]] in divided doses
'''1.2.Chronic setting''' 
* Preferred regimen: [[Hydrocortisone]] 15-25 mg/day [[Oral|PO]] divided q8-12hr (20 mg on awakening and 10 mg in the early evening)
* Alternative regimen: [[Prednisone]] (5 mg on awakening and 2.5 mg in the early evening)
'''Note'''  
*Dosage is increased in patients with severe deficiency, increased body weight, and in times of [[surgery]], [[illness]], [[Procedure|procedures]], and other [[Stress|stresses]].
*There is no established test to assess adequate [[Hormone replacement therapy|hormonal replacement]]. [[Plasma]] [[Adrenocorticotropic hormone|ACTH]] measurement and [[serum]]/[[Saliva|salivary]]/[[urinary]] [[Cortisol|cortiso]]<nowiki/>l values are all unreliable. So assessment of adequate [[Hormone|hormonal]] replacement is based on [[clinical]] basis with [[Cushingoid appearance|cushingoid features]] showing excessive replacement while [[symptoms]] of [[adrenal insufficiency]] suggesting an insufficient [[hormonal]] replacement.
*[[Glucocorticoid]] replacement can cause [[polyuria]] due to unmasking of underlying [[central diabetes insipidus]]. [[DDAVP]] is the treatment of choice for patients with [[Diabetes insipidus|diabetes insipidus (DI).]]<ref name="pmid18797595">{{cite journal |vauthors=Soares DV, Conceição FL, Vaisman M |title=[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome] |language=Portuguese |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=5 |pages=872–8 |year=2008 |pmid=18797595 |doi= |url=}}</ref>
*[[Mineralocorticoids]] are rarely required, as [[aldosterone]] secretion is primarily regulated by [[angiotensin II]] and [[potassium]], not by [[Adrenocorticotropic hormone|ACTH]].


==== Acute setting ====
==='''2. TSH deficiency'''===
* Preferred regimen: [[Hydrocortisone]] 100 mg IV bolus, then 300 mg/day IV divided q8hr '''or''' continuous infusion for 48 hours
** Once patient is stable: 50 mg PO q8hr for 6 doses, later on tapered to 30-50 mg/day PO in divided doses
'''Chronic setting''' 
* Preferred regimen: [[Hydrocortisone]] 15-25 mg/day PO divided q8-12hr
'''NOTE'''
*Dosage is increased in patients with severe deficiency, increased body weight and in times of [[surgery]], [[illness]], [[Procedure|procedures]], and other [[Stress|stresses]].
*Unfortunately, there is no established test to assess adequate [[Hormone replacement therapy|hormonal replacement]]. Plasma [[Adrenocorticotropic hormone|ACTH]] measurement and [[serum]]/[[Saliva|salivary]]/[[urinary]] [[Cortisol|cortiso]]<nowiki/>l values are all unreliable. So assessment of adequate hormonal replacement is based on [[clinical]] basis with [[Cushingoid appearance|Cushingoid features]] showing excessive replacement while [[symptoms]] of [[adrenal insufficiency]] suggesting insufficient hormonal replacement.
*[[Glucocorticoid]] replacement can cause [[polyuria]] due to unmasking of underlying [[central diabetes insipidus]]. [[DDAVP]] is the treatment of choice for patients with [[Diabetes insipidus|DI]].<ref name="pmid18797595">{{cite journal |vauthors=Soares DV, Conceição FL, Vaisman M |title=[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome] |language=Portuguese |journal=Arq Bras Endocrinol Metabol |volume=52 |issue=5 |pages=872–8 |year=2008 |pmid=18797595 |doi= |url=}}</ref>
*[[Mineralocorticoids]] are rarely required as [[aldosterone]] secretion is primarily regulated by [[angiotensin II]] and [[potassium]] not by [[Adrenocorticotropic hormone|ACTH]].


=== '''TSH deficiency''' ===
====2.1. Mild hypothyroidism====
* Preferred regimen: [[Levothyroxine]] 1.7 mcg/kg daily '''or''' 100-125 mcg [[Oral|PO]] daily.<ref name="pmid9672293">{{cite journal |vauthors=Lamberts SW, de Herder WW, van der Lely AJ |title=Pituitary insufficiency |journal=Lancet |volume=352 |issue=9122 |pages=127–34 |year=1998 |pmid=9672293 |doi= |url=}}</ref>


==== Mild hypothyroidism ====
==== 2.2. Severe hypothyroidism ====
* [[Levothyroxine]] 1.7 mcg/kg qDay '''or''' 100-125 mcg PO qDay
* Preferred regimen: [[Levothyroxine]] 12.5-25 mcg [[Oral|PO]] daily and later can be adjusted by 25 mcg/day q2-4 Week PRN.


==== Severe hypothyroidism ====
==== Note ====
* [[Levothyroxine]] 12.5-25 mcg PO qDay and later on dose can be adjusted by 25 mcg/day q2-4 Week PRN
 
==== NOTE ====
*In patients with combined [[hypothyroidism]] and [[hypocortisolism]], [[glucocorticoids]] ([[physiologic]] [[doses]] and increased doses in [[stress]]) are replaced before [[thyroid hormone]] replacement, because treating the [[hypothyroidism]] alone by [[levothyroxine]] can worsen the severity of [[Cortisol|cortiso]]<nowiki/>l deficiency by increasing the [[Clearance (medicine)|clearance]] of [[cortisol]]. So, it is important to assess [[adrenal]] function, including [[corticotropin]] ([[Adrenocorticotropic hormone|ACTH]]) reserve, before administering [[T4]] ([[levothyroxine]]).
*In patients with combined [[hypothyroidism]] and [[hypocortisolism]], [[glucocorticoids]] ([[physiologic]] [[doses]] and increased doses in [[stress]]) are replaced before [[thyroid hormone]] replacement, because treating the [[hypothyroidism]] alone by [[levothyroxine]] can worsen the severity of [[Cortisol|cortiso]]<nowiki/>l deficiency by increasing the [[Clearance (medicine)|clearance]] of [[cortisol]]. So, it is important to assess [[adrenal]] function, including [[corticotropin]] ([[Adrenocorticotropic hormone|ACTH]]) reserve, before administering [[T4]] ([[levothyroxine]]).
*American Thyroid Association (ATA) recommends dose adjustment to keep serum [[free T4]] [[concentration]] in upper half of [[reference range]].
*American Thyroid Association (ATA) recommends dose adjustment to keep serum [[free T4]] [[concentration]] in upper half of [[reference range]].


=== '''LH and FSH deficiency''' ===
==='''3. Gonadotropin deficiency'''===
* '''If fertility required:'''  
*[[Gonadotropin]] deficiency may be confirmed by measuring [[serum]] [[estradiol]], [[testosterone]], and [[FSH]]/[[LH]] levels.<ref name="pmid7705324">{{cite journal |vauthors=Matsumoto AM |title=Hormonal therapy of male hypogonadism |journal=Endocrinol. Metab. Clin. North Am. |volume=23 |issue=4 |pages=857–75 |year=1994 |pmid=7705324 |doi= |url=}}</ref<nowiki><ref name="pmid9253305"></nowiki>{{cite journal |vauthors=Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E |title=Long-term effect of testosterone therapy on bone mineral density in hypogonadal men |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=8 |pages=2386–90 |year=1997 |pmid=9253305 |doi=10.1210/jcem.82.8.4163 |url=}}</ref><ref name="pmid11401611">{{cite journal |vauthors=Torgerson DJ, Bell-Syer SE |title=Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials |journal=JAMA |volume=285 |issue=22 |pages=2891–7 |year=2001 |pmid=11401611 |doi= |url=}}</ref><ref name="pmid12864790">{{cite journal |vauthors=Armitage M, Nooney J, Evans S |title=Recent concerns surrounding HRT |journal=Clin. Endocrinol. (Oxf) |volume=59 |issue=2 |pages=145–55 |year=2003 |pmid=12864790 |doi= |url=}}</ref><ref name="pmid12007911">{{cite journal |vauthors=Braunstein GD |title=Androgen insufficiency in women: summary of critical issues |journal=Fertil. Steril. |volume=77 Suppl 4 |issue= |pages=S94–9 |year=2002 |pmid=12007911 |doi= |url=}}</ref><ref name="pmid9758439">{{cite journal |vauthors=Büchter D, Behre HM, Kliesch S, Nieschlag E |title=Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases |journal=Eur. J. Endocrinol. |volume=139 |issue=3 |pages=298–303 |year=1998 |pmid=9758439 |doi= |url=}}</ref><ref name="pmid1743320">{{cite journal |vauthors=Shoham Z, Balen A, Patel A, Jacobs HS |title=Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients |journal=Fertil. Steril. |volume=56 |issue=6 |pages=1048–53 |year=1991 |pmid=1743320 |doi= |url=}}</ref><ref name="pmid3539644">{{cite journal |vauthors=Morris DV, Abdulwahid NA, Armar A, Jacobs HS |title=The response of patients with organic hypothalamic-pituitary disease to pulsatile gonadotropin-releasing hormone therapy |journal=Fertil. Steril. |volume=47 |issue=1 |pages=54–9 |year=1987 |pmid=3539644 |doi= |url=}}</ref>
 
=== 3.1. Men ===
* Preferred regimen (1): [[Testosterone]] esters (for example, [[Sustanon]]'')  250 mg IM every 2–3 weeks''
* Alternative regimen (1): [[Transdermal]] [[testosterone]]
** Patch (for example, Andropatch)  2.5–7.5 mg/24 hours
** Gel (for example, Testogel) 5–10 g gel/24 hours
 
* Alternative regimen (2): [[Testosterone]] [[implant]]  600–800 mg every 4–6 months
* Alternative regimen (3): [[Buccal]] [[testosterone]] (for example, Striant SR)  1 [[buccal]] tablet (30 mg) applied to the gum q12h
* Alternative regimen (4): Oral [[testosterone]] (for example, Restandol)  40–120 mg daily
 
==== Note ====
* [[Intramuscular]] route administration may result in a transient increase in serum [[testosterone]] concentrations leading to low [[HDL]]-[[cholesterol]] levels.
* [[Transdermal]] route administration may result in achieving normal [[physiologic]] levels but it is being tested.<ref name="pmid3793849">{{cite journal |vauthors=Findlay JC, Place VA, Snyder PJ |title=Transdermal delivery of testosterone |journal=J. Clin. Endocrinol. Metab. |volume=64 |issue=2 |pages=266–8 |year=1987 |pmid=3793849 |doi=10.1210/jcem-64-2-266 |url=}}</ref><ref name="pmid3379703">{{cite journal |vauthors=Carey PO, Howards SS, Vance ML |title=Transdermal testosterone treatment of hypogonadal men |journal=J. Urol. |volume=140 |issue=1 |pages=76–9 |year=1988 |pmid=3379703 |doi= |url=}}</ref>
 
=== 3.2. Women ===
* Preferred regimen (1): [[Conjugated estrogens (oral)|Conjugated equine estrogens]]  0.625–1.25 mg PO daily
 
* Alternative regimen (1): [[Estradiol valerate]]  1–2 mg PO daily
* Alternative regimen (2):  [[Estradiol Patch|Estradiol (patch)]]  25–100 μg [[transdermal]] daily
* Alternative regimen (3): [[Estrogen]] plus [[progesterone]] (cyclical/continuous):  Dose depends on preparation—PO or transdermal
 
==== Note ====
* '''If fertility required'''  
** Such women are offered [[ovulation]] induction. [[Pregnancy]] can be made possible by giving [[exogenous]] [[gonadotropins]] or [[Gonadotropin-releasing hormone|pulsatile GnRH]].
** Such women are offered [[ovulation]] induction. [[Pregnancy]] can be made possible by giving [[exogenous]] [[gonadotropins]] or [[Gonadotropin-releasing hormone|pulsatile GnRH]].
** Women with [[GnRH|GnRH deficiency]] can be offered either [[Gonadotropin-releasing hormone|pulsatile GnRH]] or [[gonadotropin]] [[therapy]].
** Women with [[GnRH|GnRH deficiency]] can be offered either [[Gonadotropin-releasing hormone|pulsatile GnRH]] or [[gonadotropin]] [[therapy]].
** Women with [[gonadotropin]] deficiency are given [[gonadotropins]] only.
** Women with [[gonadotropin]] deficiency are given [[gonadotropins]] only.


* '''If fertility not required:'''
* '''If fertility not required'''
** Such women are treated with [[Estrogen and Progestin (Hormone Replacement Therapy) (patient information)|estrogen-progestin replacement therapy]] by using the traditional regimen of [[estradiol]] on days 1 through 25 of each month and [[progesterone]] on days 16 through 25 of each month.  
** Such women are treated with [[Estrogen and Progestin (Hormone Replacement Therapy) (patient information)|estrogen-progestin replacement therapy]] by using the traditional regimen of [[estradiol]] on days 1 through 25 of each month and [[progesterone]] on days 16 through 25 of each month.  
** Another regimen includes continuous [[transdermal]] [[estradiol]] throughout the month, with [[progestin]] added days 1 to 10 of the calendar month.
** Another regimen includes continuous [[transdermal]] [[estradiol]] throughout the month, with [[progestin]] added days 1 to 10 of the calendar month.
** For further information regarding the indications, contraindications and adverse effects of gonadotropin replacement therapy click [[Hypogonadism medical therapy#Medical Therapy|here]].


=== '''Androgen replacement''' ===
=== '''3.3. Androgen replacement''' ===
*[[Androgens]] can be given to females having low [[libido]].<ref name="pmid28615049">{{cite journal |vauthors=Matsuzaki S, Endo M, Ueda Y, Mimura K, Kakigano A, Egawa-Takata T, Kumasawa K, Yoshino K, Kimura T |title=A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage |journal=BMC Pregnancy Childbirth |volume=17 |issue=1 |pages=188 |year=2017 |pmid=28615049 |pmc=5471854 |doi=10.1186/s12884-017-1380-y |url=}}</ref>
*Preferred regimen (1): [[Androgens]] can be given to females having low [[libido]].<ref name="pmid28615049">{{cite journal |vauthors=Matsuzaki S, Endo M, Ueda Y, Mimura K, Kakigano A, Egawa-Takata T, Kumasawa K, Yoshino K, Kimura T |title=A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage |journal=BMC Pregnancy Childbirth |volume=17 |issue=1 |pages=188 |year=2017 |pmid=28615049 |pmc=5471854 |doi=10.1186/s12884-017-1380-y |url=}}</ref>


=== '''Growth hormone replacement''' ===
==='''4. Growth hormone replacement'''===  
*Preferred regimen (1): [[Growth hormone]] 0.27–0.7 mg SC in the evening
*[[Growth hormone|GH]] is replaced on case to case basis starting with a low dose (0.1-0.3 mg/day) and [[Titrate|titrated]] upwards by 0.1 mg/d/month with repeated measurement of [[hormone]] levels every month, initially for the first 6 months followed by yearly measurements; replaced once all other [[hormones]] have been replaced.<ref name="pmid20944496">{{cite journal |vauthors=Tessnow AH, Wilson JD |title=The changing face of Sheehan's syndrome |journal=Am. J. Med. Sci. |volume=340 |issue=5 |pages=402–6 |year=2010 |pmid=20944496 |doi=10.1097/MAJ.0b013e3181f8c6df |url=}}</ref>
*[[Growth hormone|GH]] is replaced on case to case basis starting with a low dose (0.1-0.3 mg/day) and [[Titrate|titrated]] upwards by 0.1 mg/d/month with repeated measurement of [[hormone]] levels every month, initially for the first 6 months followed by yearly measurements; replaced once all other [[hormones]] have been replaced.<ref name="pmid20944496">{{cite journal |vauthors=Tessnow AH, Wilson JD |title=The changing face of Sheehan's syndrome |journal=Am. J. Med. Sci. |volume=340 |issue=5 |pages=402–6 |year=2010 |pmid=20944496 |doi=10.1097/MAJ.0b013e3181f8c6df |url=}}</ref>
*[[Growth hormone]] is usually replaced in children and replaced in adults only if [[symptomatic]] and after all other hormones have been replaced.<ref name="pmid9467545">{{cite journal |vauthors= |title=Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency |journal=J. Clin. Endocrinol. Metab. |volume=83 |issue=2 |pages=379–81 |year=1998 |pmid=9467545 |doi=10.1210/jcem.83.2.4611 |url=}}</ref><ref name="pmid7758433">{{cite journal |vauthors=de Boer H, Blok GJ, Van der Veen EA |title=Clinical aspects of growth hormone deficiency in adults |journal=Endocr. Rev. |volume=16 |issue=1 |pages=63–86 |year=1995 |pmid=7758433 |doi=10.1210/edrv-16-1-63 |url=}}</ref><ref name="pmid9467546">{{cite journal |vauthors=Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sönksen PH, Tanaka T, Thorne M |title=Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee |journal=J. Clin. Endocrinol. Metab. |volume=83 |issue=2 |pages=382–95 |year=1998 |pmid=9467546 |doi=10.1210/jcem.83.2.4594 |url=}}</ref><ref name="pmid10341850">{{cite journal |vauthors=Beshyah SA, Johnston DG |title=Cardiovascular disease and risk factors in adults with hypopituitarism |journal=Clin. Endocrinol. (Oxf) |volume=50 |issue=1 |pages=1–15 |year=1999 |pmid=10341850 |doi= |url=}}</ref><ref name="pmid10519899">{{cite journal |vauthors=Vance ML, Mauras N |title=Growth hormone therapy in adults and children |journal=N. Engl. J. Med. |volume=341 |issue=16 |pages=1206–16 |year=1999 |pmid=10519899 |doi=10.1056/NEJM199910143411607 |url=}}</ref><ref name="pmid11344173">{{cite journal |vauthors= |title=Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=5 |pages=1868–70 |year=2001 |pmid=11344173 |doi=10.1210/jcem.86.5.7471 |url=}}</ref>
*Growth hormone replacement is found to be associated with reduced adipose tissue, increased muscle mass, strength, bone density and improved exercise tolerance<ref name="pmid2566779">{{cite journal |vauthors=Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS |title=Beneficial effects of growth hormone treatment in GH-deficient adults |journal=Lancet |volume=1 |issue=8649 |pages=1221–5 |year=1989 |pmid=2566779 |doi= |url=}}</ref><ref name="pmid2687691">{{cite journal |vauthors=Salomon F, Cuneo RC, Hesp R, Sönksen PH |title=The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency |journal=N. Engl. J. Med. |volume=321 |issue=26 |pages=1797–803 |year=1989 |pmid=2687691 |doi=10.1056/NEJM198912283212605 |url=}}</ref><ref name="pmid2022560">{{cite journal |vauthors=Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH |title=Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength |journal=J. Appl. Physiol. |volume=70 |issue=2 |pages=688–94 |year=1991 |pmid=2022560 |doi= |url=}}</ref><ref name="pmid2022561">{{cite journal |vauthors=Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH |title=Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance |journal=J. Appl. Physiol. |volume=70 |issue=2 |pages=695–700 |year=1991 |pmid=2022561 |doi= |url=}}</ref><ref name="pmid1759534">{{cite journal |vauthors=Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Møller J, Müller J, Skakkebaek NE, Christiansen JS |title=Long-term growth hormone treatment in growth hormone deficient adults |journal=Acta Endocrinol. |volume=125 |issue=5 |pages=449–53 |year=1991 |pmid=1759534 |doi= |url=}}</ref>
*For more information on GH replacement and complications associated with over-replacement, click [[Growth hormone deficiency medical therapy#Medical Therapy|here]].
*Complications of growth hormone replacement therapy:<ref name="pmid16456485">{{cite journal| author=Bowlby DA, Rapaport R| title=Safety and efficacy of growth hormone therapy in childhood. | journal=Pediatr Endocrinol Rev | year= 2004 | volume= 2 Suppl 1 | issue=  | pages= 68-77 | pmid=16456485 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16456485  }} </ref>
**[[Pseudotumor cerebri]]
**[[Intracranial hypertension|Benign intracranial hypertension.]]
**Slipped capital femoral [[epiphyses]].
**[[Diabetes mellitus]] due to [[insulin resistance]].


=== '''Prolactin deficiency''' ===
=== 5. ADH deficiency ===
* A study was done on 5 women with [[prolactin]] deficiency caused by Sheehan's syndrome or other causes that showed increased milk production upon [[subcutaneous]] administration of r-hPRL ([[recombinant]] human [[prolactin]]) every 12 hours for 28 days.<ref name="pmid20718766">{{cite journal |vauthors=Powe CE, Allen M, Puopolo KM, Merewood A, Worden S, Johnson LC, Fleischman A, Welt CK |title=Recombinant human prolactin for the treatment of lactation insufficiency |journal=Clin. Endocrinol. (Oxf) |volume=73 |issue=5 |pages=645–53 |year=2010 |pmid=20718766 |doi=10.1111/j.1365-2265.2010.03850.x |url=}}</ref>
* Preferred regimen (1): [[Desmopressin]]  300–600 μg PO daily in 2–3 divided doses '''OR''' 10–40 μg [[intranasally]] daily in 2–3 divided doses
 
=== '''6. Prolactin deficiency''' ===
* There is no synthetic commercial preparation available to replace [[prolactin]].
* A study was done on 5 women with [[prolactin]] deficiency caused by [[Sheehan's syndrome]] or other causes that showed increased milk production upon [[subcutaneous]] administration of r-hPRL ([[recombinant]] human [[prolactin]]) every 12 hours for 28 days.<ref name="pmid20718766">{{cite journal |vauthors=Powe CE, Allen M, Puopolo KM, Merewood A, Worden S, Johnson LC, Fleischman A, Welt CK |title=Recombinant human prolactin for the treatment of lactation insufficiency |journal=Clin. Endocrinol. (Oxf) |volume=73 |issue=5 |pages=645–53 |year=2010 |pmid=20718766 |doi=10.1111/j.1365-2265.2010.03850.x |url=}}</ref>


==References==
==References==
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[[Category:Medicine]]
[[Category:Endocrinology]]
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Latest revision as of 22:19, 29 July 2020

Hypopituitarism Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

The mainstay of treatment for hypopituitarism is hormone replacement therapy and treating the underlying cause. Adrenocorticotrophic hormone (ACTH) deficiency is treated with glucocorticoids. Gonadotropin deficiency is treated with testosterone in men and estrogen with or without progesterone in women. Hypothyroidism is treated with levothyroxine. Growth hormone (GH) is usually replaced in children and replaced in adults only if symptomatic and after replacement of all other pituitary hormones.

Medical Therapy

1.ACTH deficiency

[15][16][17][7][18][19]

1.1.Acute setting

  • Preferred regimen: Hydrocortisone 100 mg IV bolus, then 300 mg/day IV divided q8hr or continuous infusion for 48 hours
    • Once patient is stable: 50 mg PO q8hr for 6 doses, later on tapered to 30-50 mg/day PO in divided doses

1.2.Chronic setting

  • Preferred regimen: Hydrocortisone 15-25 mg/day PO divided q8-12hr (20 mg on awakening and 10 mg in the early evening)
  • Alternative regimen: Prednisone (5 mg on awakening and 2.5 mg in the early evening)

Note

2. TSH deficiency

2.1. Mild hypothyroidism

2.2. Severe hypothyroidism

  • Preferred regimen: Levothyroxine 12.5-25 mcg PO daily and later can be adjusted by 25 mcg/day q2-4 Week PRN.

Note

3. Gonadotropin deficiency

3.1. Men

  • Preferred regimen (1): Testosterone esters (for example, Sustanon) 250 mg IM every 2–3 weeks
  • Alternative regimen (1): Transdermal testosterone
    • Patch (for example, Andropatch) 2.5–7.5 mg/24 hours
    • Gel (for example, Testogel) 5–10 g gel/24 hours
  • Alternative regimen (2): Testosterone implant 600–800 mg every 4–6 months
  • Alternative regimen (3): Buccal testosterone (for example, Striant SR) 1 buccal tablet (30 mg) applied to the gum q12h
  • Alternative regimen (4): Oral testosterone (for example, Restandol) 40–120 mg daily

Note

3.2. Women

Note

  • If fertility not required
    • Such women are treated with estrogen-progestin replacement therapy by using the traditional regimen of estradiol on days 1 through 25 of each month and progesterone on days 16 through 25 of each month.
    • Another regimen includes continuous transdermal estradiol throughout the month, with progestin added days 1 to 10 of the calendar month.
    • For further information regarding the indications, contraindications and adverse effects of gonadotropin replacement therapy click here.

3.3. Androgen replacement

4. Growth hormone replacement

5. ADH deficiency

  • Preferred regimen (1): Desmopressin 300–600 μg PO daily in 2–3 divided doses OR 10–40 μg intranasally daily in 2–3 divided doses

6. Prolactin deficiency

References

  1. ↑ Parikh R, Buch V, Makwana M, Buch HN (2016). "The price of a 15-year delay in diagnosis of Sheehan's syndrome". Proc (Bayl Univ Med Cent). 29 (2): 212–3. PMC 4790577. PMID 27034575.
  2. ↑ Laway BA, Bhat JR, Mir SA, Khan RS, Lone MI, Zargar AH (2010). "Sheehan's syndrome with pancytopenia--complete recovery after hormone replacement (case series with review)". Ann. Hematol. 89 (3): 305–8. doi:10.1007/s00277-009-0804-9. PMID 19697029.
  3. ↑ Tanriverdi F, Unluhizarci K, Kula M, Guven M, Bayram F, Kelestimur F (2005). "Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome". Growth Horm. IGF Res. 15 (3): 231–7. doi:10.1016/j.ghir.2005.03.005. PMID 15921942.
  4. ↑ Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM (1997). "Increased cerebrovascular mortality in patients with hypopituitarism". Clin. Endocrinol. (Oxf). 46 (1): 75–81. PMID 9059561.
  5. ↑ Arafah BM (2002). "Medical management of hypopituitarism in patients with pituitary adenomas". Pituitary. 5 (2): 109–17. PMID 12675508.
  6. ↑ Grossman AB (2010). "Clinical Review#: The diagnosis and management of central hypoadrenalism". J. Clin. Endocrinol. Metab. 95 (11): 4855–63. doi:10.1210/jc.2010-0982. PMID 20719838.
  7. ↑ 7.0 7.1 Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, Loriaux DL (1991). "Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry". J. Clin. Endocrinol. Metab. 72 (1): 39–45. doi:10.1210/jcem-72-1-39. PMID 1986026.
  8. ↑ Arlt W, Rosenthal C, Hahner S, Allolio B (2006). "Quality of glucocorticoid replacement in adrenal insufficiency: clinical assessment vs. timed serum cortisol measurements". Clin. Endocrinol. (Oxf). 64 (4): 384–9. doi:10.1111/j.1365-2265.2006.02473.x. PMID 16584509.
  9. ↑ Thomson AH, Devers MC, Wallace AM, Grant D, Campbell K, Freel M, Connell JM (2007). "Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency". Clin. Endocrinol. (Oxf). 66 (6): 789–96. doi:10.1111/j.1365-2265.2007.02812.x. PMID 17437510.
  10. ↑ Martin MM (1969). "Coexisting anterior pituitary and neurohypophyseal insufficiency. A syndrome with diagnostic implication". Arch. Intern. Med. 123 (4): 409–16. PMID 4182323.
  11. ↑ Shibata H, Ogishima T, Mitani F, Suzuki H, Murakami M, Saruta T, Ishimura Y (1991). "Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium". Endocrinology. 128 (5): 2534–9. doi:10.1210/endo-128-5-2534. PMID 2019265.
  12. ↑ White PC (1994). "Disorders of aldosterone biosynthesis and action". N. Engl. J. Med. 331 (4): 250–8. doi:10.1056/NEJM199407283310408. PMID 8015573.
  13. ↑ Miller KK, Sesmilo G, Schiller A, Schoenfeld D, Burton S, Klibanski A (2001). "Androgen deficiency in women with hypopituitarism". J. Clin. Endocrinol. Metab. 86 (2): 561–7. doi:10.1210/jcem.86.2.7246. PMID 11158009.
  14. ↑ Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A (2006). "Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study". J. Clin. Endocrinol. Metab. 91 (5): 1683–90. doi:10.1210/jc.2005-2596. PMID 16478814.
  15. ↑ Peacey SR, Guo CY, Robinson AM, Price A, Giles MA, Eastell R, Weetman AP (1997). "Glucocorticoid replacement therapy: are patients over treated and does it matter?". Clin. Endocrinol. (Oxf). 46 (3): 255–61. PMID 9156031.
  16. ↑ Arlt W, Allolio B (2003). "Adrenal insufficiency". Lancet. 361 (9372): 1881–93. doi:10.1016/S0140-6736(03)13492-7. PMID 12788587.
  17. ↑ Howlett TA (1997). "An assessment of optimal hydrocortisone replacement therapy". Clin. Endocrinol. (Oxf). 46 (3): 263–8. PMID 9156032.
  18. ↑ Besser GM, Jeffcoate WJ (1976). "Endocrine and metabolic diseases. Adrenal diseases". Br Med J. 1 (6007): 448–51. PMC 1638946. PMID 3256.
  19. ↑ Peacey SR, Pope RM, Naik KS, Hardern RD, Page MD, Belchetz PE (1993). "Corticosteroid therapy and intercurrent illness: the need for continuing patient education". Postgrad Med J. 69 (810): 282–4. PMC 2399661. PMID 8321791.
  20. ↑ Soares DV, Conceição FL, Vaisman M (2008). "[Clinical, laboratory and therapeutics aspects of Sheehan's syndrome]". Arq Bras Endocrinol Metabol (in Portuguese). 52 (5): 872–8. PMID 18797595.
  21. ↑ Lamberts SW, de Herder WW, van der Lely AJ (1998). "Pituitary insufficiency". Lancet. 352 (9122): 127–34. PMID 9672293.
  22. ↑ Matsumoto AM (1994). "Hormonal therapy of male hypogonadism". Endocrinol. Metab. Clin. North Am. 23 (4): 857–75. PMID 7705324.</ref<ref name="pmid9253305">Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E (1997). "Long-term effect of testosterone therapy on bone mineral density in hypogonadal men". J. Clin. Endocrinol. Metab. 82 (8): 2386–90. doi:10.1210/jcem.82.8.4163. PMID 9253305.
  23. ↑ Torgerson DJ, Bell-Syer SE (2001). "Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials". JAMA. 285 (22): 2891–7. PMID 11401611.
  24. ↑ Armitage M, Nooney J, Evans S (2003). "Recent concerns surrounding HRT". Clin. Endocrinol. (Oxf). 59 (2): 145–55. PMID 12864790.
  25. ↑ Braunstein GD (2002). "Androgen insufficiency in women: summary of critical issues". Fertil. Steril. 77 Suppl 4: S94–9. PMID 12007911.
  26. ↑ Büchter D, Behre HM, Kliesch S, Nieschlag E (1998). "Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases". Eur. J. Endocrinol. 139 (3): 298–303. PMID 9758439.
  27. ↑ Shoham Z, Balen A, Patel A, Jacobs HS (1991). "Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients". Fertil. Steril. 56 (6): 1048–53. PMID 1743320.
  28. ↑ Morris DV, Abdulwahid NA, Armar A, Jacobs HS (1987). "The response of patients with organic hypothalamic-pituitary disease to pulsatile gonadotropin-releasing hormone therapy". Fertil. Steril. 47 (1): 54–9. PMID 3539644.
  29. ↑ Findlay JC, Place VA, Snyder PJ (1987). "Transdermal delivery of testosterone". J. Clin. Endocrinol. Metab. 64 (2): 266–8. doi:10.1210/jcem-64-2-266. PMID 3793849.
  30. ↑ Carey PO, Howards SS, Vance ML (1988). "Transdermal testosterone treatment of hypogonadal men". J. Urol. 140 (1): 76–9. PMID 3379703.
  31. ↑ Matsuzaki S, Endo M, Ueda Y, Mimura K, Kakigano A, Egawa-Takata T, Kumasawa K, Yoshino K, Kimura T (2017). "A case of acute Sheehan's syndrome and literature review: a rare but life-threatening complication of postpartum hemorrhage". BMC Pregnancy Childbirth. 17 (1): 188. doi:10.1186/s12884-017-1380-y. PMC 5471854. PMID 28615049.
  32. ↑ Tessnow AH, Wilson JD (2010). "The changing face of Sheehan's syndrome". Am. J. Med. Sci. 340 (5): 402–6. doi:10.1097/MAJ.0b013e3181f8c6df. PMID 20944496.
  33. ↑ "Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency". J. Clin. Endocrinol. Metab. 83 (2): 379–81. 1998. doi:10.1210/jcem.83.2.4611. PMID 9467545.
  34. ↑ de Boer H, Blok GJ, Van der Veen EA (1995). "Clinical aspects of growth hormone deficiency in adults". Endocr. Rev. 16 (1): 63–86. doi:10.1210/edrv-16-1-63. PMID 7758433.
  35. ↑ Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sönksen PH, Tanaka T, Thorne M (1998). "Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee". J. Clin. Endocrinol. Metab. 83 (2): 382–95. doi:10.1210/jcem.83.2.4594. PMID 9467546.
  36. ↑ Beshyah SA, Johnston DG (1999). "Cardiovascular disease and risk factors in adults with hypopituitarism". Clin. Endocrinol. (Oxf). 50 (1): 1–15. PMID 10341850.
  37. ↑ Vance ML, Mauras N (1999). "Growth hormone therapy in adults and children". N. Engl. J. Med. 341 (16): 1206–16. doi:10.1056/NEJM199910143411607. PMID 10519899.
  38. ↑ "Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society". J. Clin. Endocrinol. Metab. 86 (5): 1868–70. 2001. doi:10.1210/jcem.86.5.7471. PMID 11344173.
  39. ↑ Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS (1989). "Beneficial effects of growth hormone treatment in GH-deficient adults". Lancet. 1 (8649): 1221–5. PMID 2566779.
  40. ↑ Salomon F, Cuneo RC, Hesp R, Sönksen PH (1989). "The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency". N. Engl. J. Med. 321 (26): 1797–803. doi:10.1056/NEJM198912283212605. PMID 2687691.
  41. ↑ Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH (1991). "Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength". J. Appl. Physiol. 70 (2): 688–94. PMID 2022560.
  42. ↑ Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH (1991). "Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance". J. Appl. Physiol. 70 (2): 695–700. PMID 2022561.
  43. ↑ Jørgensen JO, Pedersen SA, Thuesen L, Jørgensen J, Møller J, Müller J, Skakkebaek NE, Christiansen JS (1991). "Long-term growth hormone treatment in growth hormone deficient adults". Acta Endocrinol. 125 (5): 449–53. PMID 1759534.
  44. ↑ Bowlby DA, Rapaport R (2004). "Safety and efficacy of growth hormone therapy in childhood". Pediatr Endocrinol Rev. 2 Suppl 1: 68–77. PMID 16456485.
  45. ↑ Powe CE, Allen M, Puopolo KM, Merewood A, Worden S, Johnson LC, Fleischman A, Welt CK (2010). "Recombinant human prolactin for the treatment of lactation insufficiency". Clin. Endocrinol. (Oxf). 73 (5): 645–53. doi:10.1111/j.1365-2265.2010.03850.x. PMID 20718766.

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