Hypopituitarism differential diagnosis
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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], Ahmed Elsaiey, MBBCH [3]
Overview
Hypopituitarism must be differentiated from Sheehan's syndrome, lymphocytic hypophysitis, pituitary apoplexy, hypothyroidism, Addison's disease, empty sella syndrome, hypogonadotropic hypogonadism, Simmonds' disease, hypoprolactinemia, and menopause.
Differentiating Hypopituitarism from other Diseases
- For the differential of hypopituitarism on the basis of thyroid hormone deficiency, click here.
- For the differential of hypopituitarism on the basis of panhypopituitarism, click here.
- For the differential of hypopituitarism on the basis of panhypopituitarism, click here.
- For the differential of hypopituitarism on the basis of panhypopituitarism, click here.
Differentiating various causes of Panhypopituitarism
Hypopituitarism should be differentiated from other diseases like Sheehan's syndrome, lymphocytic hypophysitis, pituitary apoplexy, hypothyroidism, Addison's disease, empty sella syndrome, hypogonadotropic hypogonadism, Simmonds' disease, hypoprolactinemia, and menopause.[1][2][3][4][5][6][7]
Diseases | Onset | Manifestations | Diagnosis | |||||||
---|---|---|---|---|---|---|---|---|---|---|
History and Symptoms | Physical examination | Laboratory findings | Gold standard | Imaging | Other investigation findings | |||||
Trumatic delivery | Lactation failure | Menstrual irregularities | Other features | |||||||
Panhypopituitarism | Chronic | - | + | Oligo/amenorrhea |
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Sheehan's syndrome | Acute | ++ | ++ | Oligo/amenorrhea |
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CT/MRI:
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Lymphocytic hypophysitis | Acute | +/- | + | Oligo/amenorrhea |
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Assays for:
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Pituitary apoplexy | Acute | +/- | ++ | Oligo/amenorrhea | Severe headache
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Blood tests may be done to check: | ||
Empty sella syndrome | Chronic | - | + | Oligo/amenorrhea |
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Simmond's disease/Pituitary cachexia | Chronic | +/- | + | Oligo/amenorrhea |
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Differentiating different causes of hypothyroidism
Differentiating hypopituitarism from hypothyroidism that present as a single hormonal deficiency:[8][9][10]
Disease | History and symptoms | Laboratory findings | Additional findings | |||||||||
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Fever | Goiter | Pain | TSH | Free T4 | T3 | T3RU | Thyroglobin | TRH | TPOAb | |||
Primary hypothyroidism | Autoimmune | + | +/-
Diffuse |
- | ↑ | ↓ | N/↓ | Normal | N/↑ | Normal | ↑ |
|
Thyroiditis | + | +/- | + | ↑ | ↓ | Normal | Normal | N/↑ | Normal | Normal |
| |
Others | - | +/- | - | ↑ | ↓ | Normal | Normal | N/↑ | Normal | Normal |
| |
Transient hypothyroidism | +/- | - | +/- | ↑ | ↑ | Normal | Normal | ↑ | Normal | Normal |
| |
Subclinical hypothyroidism | - | - | - | ↑ | Normal | Normal | Normal | ↑ | Normal | N/↑ |
| |
Central Hypothyroidism | Pituitary | + | - | - | N/↓ | N/↓ | N/↓ | ↓ | Normal | Normal | Normal |
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Hypothalamus | + | - | - | ↑ | Normal | ↓ | Normal |
| ||||
Resistance to TSH/TRH | - | - | - | ↑ | N/↓ | N/↓ | Normal | Normal | ↑/↓ | Normal |
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Differentiating Hypogonadism from other Diseases
Hypogonadism must be differentiated from diseases that cause delayed puberty or infertility. These diseases include congenital diseases as Klinefelter syndrome, Kallmann syndrome and cryptorchidism. The diseases also include testicular torsion and orchitis in males, polycystic ovary syndrome, pelvic inflammatory disease, and endometriosis in females.
Diseases | Clinical findings | Diagnosis | Manangement | |
---|---|---|---|---|
Congenital diseases | Klinefelter syndrome | Clinical features of Klinefelter syndrome are as the following:[11]
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Kallmann syndrome | Clinical features of Kallmann syndrome include:
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Cryptorchidism | Clinical features of cryptorchidism include:[12]
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Male diseases | Testicular torsion | Patients of testicular torsion usually present with following:[13] |
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Management is mainly surgical through detorsion and fixation of the affected testes. |
Orchitis | Clincial features of orchitis include the following:[14][15]
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Female diseases | Polycystic ovarian syndrome (PCOS) | Possible clinical findings in cases of PCOS:[16] |
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Pelvic inflammatory disease | Patients usually present with the following:[18][19]
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Endometriosis | Clinical features of endometriosis include the following:[20]
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Medical therapy:
Surgery:
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Disease | Differentiating symptoms | Differentiating laboratory findings | Gold standard test | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Hypotension | Abdominal pain | Anorexia/
weight loss |
Muscle weakness | Hypoglycemia | Skin pigmentation | Other symptoms | Hyponatremia | Cortisol levels | Other labs | ||
Addison's disease | + | + | + | + | + | + | + | Low | ACTH stimulation test | ||
Myopathies
hereditary myopathies) |
- | - | - | + | - | Heliotrope rash and
Gottron's sign |
- | Normal | - | Muscle biopsy | |
Celiac disease | - | + | + | - | - | Dermatitis herpetiformis |
|
- | Normal | - | Abnormal small bowel biopsy |
Syndrome of inappropriate anti-diuretic hormone | - | - | - | - | - | - | - | + | Normal |
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Water deprivation test |
Neurofibromatosis | - | - | + | + | - | Axillary- and inguinal-area freckling |
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- | - | - | Biopsy of skin tissue |
Peutz-Jeghers syndrome | + | + |
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- | Normal | Colonic imaging showing the small intestinal polyps | |||||
Porphyria cutanea tarda | - | + | - | - | - | Blisters on sun-exposed sites |
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- | Normal or elevated | High level of porphyrins in the urine | |
Salt-depletion nephritis | + | Flank pain | - | - | - | - | + | Elevated | <15:1 BUN:CR | ||
Bronchogenic carcinoma | - | - | + | - | - | + | - | Elevated | Increased ACTH and | Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue | |
Anorexia nervosa | + | - | + | + | + | - |
|
- | Elevated | - | Psychiatric condition |
Disease | Clinical Findings | Laboratory findings | Management |
---|---|---|---|
Somatotroph adenoma: | Clinical features of acromegaly are due to high level of human growth hormone (hGH):
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Corticotroph adenoma: Cushing's syndrome | Clinical features of Cushing's syndrome are due to increased levels of cortisol:
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Hypothyroidism | Clinical features of hypothyroidism are due to deficiency of thyroxine:
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Levothyroxine |
Chronic renal failure | There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include:
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Urinalysis:
Fluid and electrolyte disturbances: Endocrine and metabolic disturbances:
Hematologic abnormalities: |
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Liver disease: Cirrhosis | The clinical features of liver cirrhosis are very nonspecific. These include:
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Seizure disorder | The clinical features of seizure disorder may include:
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Electroencephalogram |
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Medication-induced | Clinical features of hyperprolactinemia after a specific period of regular medication ingestion | Discontinuation of the medication for 3 days and remeasurement of prolactin levels[21] | Change to alternate medication |
Differentiating hypopituitarism on the basis of GH Deficiency
Diseases | History and symptoms | Physical Examination | Laboratory findings | |||||
---|---|---|---|---|---|---|---|---|
Puberty development | Height velocity | Parents height | Characteristic facies | Bone age | Genetic analysis | GH level | ||
Growth hormone deficiency[22] |
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Delayed | Decreased | Normal |
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Dlayed |
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Low |
Achondroplasia[23] |
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Normal | Decreased | Decreased |
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Delayed |
FGFR3 gene mutations |
Normal |
Familial short stature[24] |
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Normal | Decreased | Decreased | Normal | Normal | Heterozygous IGF1 Splicing mutation | Normal |
Constitutional growth delay[25] |
|
Delayed | Normal | Normal | Normal | Normal | Mutations in Variation in FGFR1, GNRHR, TAC3, and TACR3 genes | Normal |
Growth Hormone Resistance[26] |
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Delayed | Decreased | Normal |
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Delayed |
|
Normal |
Pediatric Hypothyroidism[27] |
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Delayed | Decreased | Normal |
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Delayed |
Mutations in:
|
Normal |
Turner Syndrome[28] |
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Absent | Decreased | Decreased |
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Normal | 45 X0 | Normal |
Silver-Russell Syndrome[29] |
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Delayed | Decreased | Decreased |
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Normal | Methylation involving the H19 and IGF2 genes | Normal |
Noonan Syndrome[30] | Delayed | Decreased | Decreased | Minor facial dysmorphism | Normal | PTPN11 and SOS1 genes abnormality | Normal | |
Psychosocial Short Stature[31] |
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Delayed | Decreased | Normal |
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Normal | Normal | May be low |
Short stature accompanying systemic disease[32] |
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Delayed | Decreased | Normal | Failure to thrive | Delayed | Normal | Normal |
Idiopathic short stature[33] | A height below 2 standard deviations (SD) of the mean for age, in the absence of any endocrine, metabolic, or other diagnosis | Normal | Decreased | Normal | Normal | Delayed | SHOX gene mutations[34] | Normal |
Type of DI | Subclass | Disease | Defining signs and symptoms | Lab/Imaging findings |
---|---|---|---|---|
Central | Acquired | Histiocytosis |
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Craniopharyngioma |
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Sarcoidosis |
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Congenital | Hydrocephalus |
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Dilated ventricles on CT and MRI | |
Wolfram Syndrome (DIDMOAD) |
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Nephrogenic | Acquired | Drug-induced (demeclocycline, lithium) |
| |
Hypercalcemia |
| |||
Hypokalemia |
| |||
Multiple myeloma |
|
| ||
Sickle cell disease |
|
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Primary polydipsia | Psychogenic |
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Gestational diabetes insipidus |
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Diabetes mellitus |
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References
- ↑ Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.
- ↑ Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH (1995). "Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature". Clin. Endocrinol. (Oxf). 42 (3): 315–22. PMID 7758238.
- ↑ Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, Strasburger C, Störmann S, Küppers A, Streetz-van der Werf C, Deutschbein T, Stieg M, Rotermund R, Milian M, Petersenn S (2015). "Diagnosis of Primary Hypophysitis in Germany". J. Clin. Endocrinol. Metab. 100 (10): 3841–9. doi:10.1210/jc.2015-2152. PMID 26262437.
- ↑ Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S (1995). "Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings". J. Clin. Endocrinol. Metab. 80 (8): 2302–11. doi:10.1210/jcem.80.8.7629223. PMID 7629223.
- ↑ Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H (1993). "Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus". N. Engl. J. Med. 329 (10): 683–9. doi:10.1056/NEJM199309023291002. PMID 8345854.
- ↑ Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS (2011). "Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman". Emerg Med Australas. 23 (3): 372–5. doi:10.1111/j.1742-6723.2011.01425.x. PMID 21668725.
- ↑ Dejager S, Gerber S, Foubert L, Turpin G (1998). "Sheehan's syndrome: differential diagnosis in the acute phase". J. Intern. Med. 244 (3): 261–6. PMID 9747750.
- ↑ Invalid
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- ↑ Denschlag, Dominik, MD; Clemens, Tempfer, MD; Kunze, Myriam, MD; Wolff, Gerhard, MD; Keck, Christoph, MD (October 2004), "Assisted reproductive techniques in patients with Klinefelter syndrome: A critical review", Fertility and Sterility, 82 (4): 775–779, doi:10.1016/j.fertnstert.2003.09.085
- ↑ Virtanen HE, Bjerknes R, Cortes D, Jørgensen N, Rajpert-De Meyts E, Thorsson AV; et al. (2007). "Cryptorchidism: classification, prevalence and long-term consequences". Acta Paediatr. 96 (5): 611–6. doi:10.1111/j.1651-2227.2007.00241.x. PMID 17462053.
- ↑ Schmitz D, Safranek S (2009). "Clinical inquiries. How useful is a physical exam in diagnosing testicular torsion?". J Fam Pract. 58 (8): 433–4. PMID 19679025.
- ↑ Trojian TH, Lishnak TS, Heiman D (2009). "Epididymitis and orchitis: an overview". Am Fam Physician. 79 (7): 583–7. PMID 19378875.
- ↑ Stewart A, Ubee SS, Davies H (2011). "Epididymo-orchitis". BMJ. 342: d1543. PMID 21490048.
- ↑ Christine Cortet-Rudelli, Didier Dewailly (2006). "Diagnosis of Hyperandrogenism in Female Adolescents". Hyperandrogenism in Adolescent Girls. Armenian Health Network, Health.am. Unknown parameter
|month=
ignored (help) - ↑ Legro RS, Barnhart HX, Schlaff WD (2007). "Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome". N Engl J Med. 356 (6): 551–566. PMID 17287476.
- ↑ Brunham RC, Gottlieb SL, Paavonen J (2015). "Pelvic inflammatory disease". N. Engl. J. Med. 372 (21): 2039–48. doi:10.1056/NEJMra1411426. PMID 25992748.
- ↑ Ford GW, Decker CF (2016). "Pelvic inflammatory disease". Dis Mon. 62 (8): 301–5. doi:10.1016/j.disamonth.2016.03.015. PMID 27107781.
- ↑ Murphy AA (2002). "Clinical aspects of endometriosis". Ann N Y Acad Sci. 955: 1–10, discussion 34-6, 396–406. PMID 11949938.
- ↑ Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA; et al. (2011). "Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (2): 273–88. doi:10.1210/jc.2010-1692. PMID 21296991.
- ↑ Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G; et al. (1999). "Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism". J Clin Endocrinol Metab. 84 (6): 1919–24. doi:10.1210/jcem.84.6.5742. PMID 10372687.
- ↑ Bouali H, Latrech H (2015). "Achondroplasia: Current Options and Future Perspective". Pediatr Endocrinol Rev. 12 (4): 388–95. PMID 26182483.
- ↑ Kawashima Y, Hakuno F, Okada S, Hotsubo T, Kinoshita T, Fujimoto M; et al. (2014). "Familial short stature is associated with a novel dominant-negative heterozygous insulin-like growth factor 1 receptor (IGF1R) mutation". Clin Endocrinol (Oxf). 81 (2): 312–4. doi:10.1111/cen.12317. PMID 24033502.
- ↑ Vaaralahti K, Wehkalampi K, Tommiska J, Laitinen EM, Dunkel L, Raivio T (2011). "The role of gene defects underlying isolated hypogonadotropic hypogonadism in patients with constitutional delay of growth and puberty". Fertil Steril. 95 (8): 2756–8. doi:10.1016/j.fertnstert.2010.12.059. PMID 21292259.
- ↑ Kurtoğlu S, Hatipoglu N (2016). "Growth hormone insensitivity: diagnostic and therapeutic approaches". J Endocrinol Invest. 39 (1): 19–28. doi:10.1007/s40618-015-0327-2. PMID 26062520.
- ↑ Léger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G; et al. (2014). "European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism". Horm Res Paediatr. 81 (2): 80–103. doi:10.1159/000358198. PMID 24662106.
- ↑ Trovó de Marqui AB (2015). "[Turner syndrome and genetic polymorphism: a systematic review]". Rev Paul Pediatr. 33 (3): 364–71. doi:10.1016/j.rpped.2014.11.014. PMC 4620965. PMID 25765448.
- ↑ Wakeling EL (2011). "Silver-Russell syndrome". Arch Dis Child. 96 (12): 1156–61. doi:10.1136/adc.2010.190165. PMID 21349887.
- ↑ Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R; et al. (2007). "Germline gain-of-function mutations in RAF1 cause Noonan syndrome". Nat Genet. 39 (8): 1013–7. doi:10.1038/ng2078. PMID 17603482.
- ↑ Sandberg DE, Gardner M (2015). "Short Stature: Is It a Psychosocial Problem and Does Changing Height Matter?". Pediatr Clin North Am. 62 (4): 963–82. doi:10.1016/j.pcl.2015.04.009. PMID 26210627.
- ↑ Sanderson IR (2014). "Growth problems in children with IBD". Nat Rev Gastroenterol Hepatol. 11 (10): 601–10. doi:10.1038/nrgastro.2014.102. PMID 24957008.
- ↑ Wit JM, Clayton PE, Rogol AD, Savage MO, Saenger PH, Cohen P (2008). "Idiopathic short stature: definition, epidemiology, and diagnostic evaluation". Growth Horm IGF Res. 18 (2): 89–110. doi:10.1016/j.ghir.2007.11.004. PMID 18182313.
- ↑ Ouni M, Castell AL, Rothenbuhler A, Linglart A, Bougnères P (2015). "Higher methylation of the IGF1 P2 promoter is associated with idiopathic short stature". Clin Endocrinol (Oxf). doi:10.1111/cen.12867. PMID 26218795.
- ↑ Ghosh KN, Bhattacharya A (1992). "Gonotrophic nature of Phlebotomus argentipes (Diptera: Psychodidae) in the laboratory". Rev Inst Med Trop Sao Paulo. 34 (2): 181–2. PMID 1340034.