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 panhypopituitarism, click here.
For the differential of hypopituitarism on the basis of thyroid hormone deficiency, click here.
For the differential of hypopituitarism on the basis of hypogonadism, 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	Physical examination	Laboratory findings	Gold standard	Imaging	Other investigation findings
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure B/L hemianopsia Papilledema	All pituitary hormones decreased	MRI		Left hand and wrist radiograph for bone age
Sheehan's syndrome	Acute	++	++	Oligo/amenorrhea	Adrenal insufficiency symptoms Hypothyroidism features	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Dx is clinical Most senitive test: low baseline prolactin levels w/o response to TRH	CT/MRI: Sequential changes of pituitary enlargement followed by Shrinkage and necrosis leading to decreased sellar volume or empty sella	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Mass lesion effect such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones(Gonadotropins most common) Hyperprolactinemia(40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT & MRI: Features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V , and VI)	Decreased levels of anterior pituitary hormones in blood.	MRI	CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion MRI: If inconclusive CT	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in blood.	MRI	Empty sella containing CSF	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Simmond's disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in blood.	MRI		Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Primary hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexes	Low T3,T4 High TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out any pituitary cause	Assays for anti-TPO and anti-Tg Ab FNA biopsy
Primary Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido		Low estrogen, testosterone High FSH/LH		Done to rule out any pituitary cause	Genetic tests (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertiliy	Puerperal agalactogenesis	No workup is necessary		Done to rule out any pituitary cause	Prolactin assay in 3rd trimester LH, FSH Thyrotropin and free thyroxine
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation loss of pubic and axillary hair	Hyponatremia with/without hyperkalemia Plasma renin activity to aldosterone ratio	Abdominal CT	Abdominal CT	Serum cortisol testing Serum ACTH testing Anti-adrenal Ab testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH > LH

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
Disease		Fever	Goiter	Pain	TSH	Free T4	T3	T3RU	Thyroglobin	TRH	TPOAb	Additional findings
Primary hypothyroidism	Autoimmune	+	+/- Diffuse	-	↑	↓	N/↓	Normal	N/↑	Normal	↑	May be accompanied by other autoimmune diseases
	Thyroiditis	+	+/-	+	↑	↓	Normal	Normal	N/↑	Normal	Normal	Infectious thyroiditis associated with neck pain
	Others	-	+/-	-	↑	↓	Normal	Normal	N/↑	Normal	Normal	History of hyperthyroidism Drug history
Transient hypothyroidism		+/-	-	+/-	↑	↑	Normal	Normal	↑	Normal	Normal	May present primarily with hyperthyroidism
Subclinical hypothyroidism		-	-	-	↑	Normal	Normal	Normal	↑	Normal	N/↑	Asymptomatic
Central Hypothyroidism	Pituitary	+	-	-	N/↓	N/↓	N/↓	↓	Normal	Normal	Normal	Other pituitary hormone deficiencies signs
Central Hypothyroidism	Hypothalamus	+	-	-	N/↓	N/↓	N/↓	↑	Normal	↓	Normal	Other pituitary hormone deficiencies signs
Resistance to TSH/TRH		-	-	-	↑	N/↓	N/↓	Normal	Normal	↑/↓	Normal	Rare

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] Language learning impairment. Neuropsychological testing often reveals deficits in executive functions. Delays in motor development.	Karyotyping Semen count Serum estradiol levels (a type of estrogen) Serum follicle stimulating hormone Serum luteinizing hormone Serum testosterone	Testosterone therapy may be indicated to treat the symptoms of the disease
	Kallmann syndrome	Clinical features of Kallmann syndrome include: Hypogonadism Anosmia	Serum follicle stimulating hormone Serum luteinizing hormone Serum testosterone Gonadotropin hormones	Testosterone replacement therapy Estrogen replacement therapy (in females)
	Cryptorchidism	Clinical features of cryptorchidism include:^[12] Empty scrotum Inguinal fullness	Ultrasonography may be indicated to locate the gonads	Treatment of cryptorchidism is mainly surgical in order to reduce the risk of malignancy Orchiopexy surgery is recommended in order to reposition the undecsended testes.
Male diseases	Testicular torsion	Patients of testicular torsion usually present with following:^[13] Sudden onset of severe pain in one testicle, with or without a previous predisposing event Swelling within one side of the scrotum (scrotal swelling) Nausea or vomiting Lightheadedness Bell clapper deformity of testes on examination	Scrotal ultrasound Urinalysis to exclude bacterial infection	Management is mainly surgical through detorsion and fixation of the affected testes.
Male diseases	Orchitis	Clincial features of orchitis include the following:^[14]^[15] Scrotal swelling Scrotal pain urinary tract infections Nausea, vomiting and chills Prehn's sign positive Costovertebral angle tenderness Fever	Urethral Gram stain Urinalysis Urine culture PCR to detect the presence of Neisseria gonorrheae and Chlamydia trachomatis Scrotal ultrasound is the diagnostic imaging of choice in cases of acute scrotum.	Bed rest and limitation of physical activity Use of cold packs Analgesia Non-steroidal anti-inflammatory drugs (NSAIDs) Levofloxacin in bacterial infeciton.
Female diseases	Polycystic ovarian syndrome (PCOS)	Possible clinical findings in cases of PCOS:^[16] Amenorrhea Oligoamenorrhea Ovarian cysts Pelvic pain Dysparuenia Acne Hirsutism Anxiety and depression Sleep apnea	Blood testosterone level LH and FSH levels Pelvic ultrasound	Clomiphene citrate and metformin to manage infertility.^[17] Cyproterone acetate for the treatment of acne and hirsutism. Spironolactone
	Pelvic inflammatory disease	Patients usually present with the following:^[18]^[19] Bilateral abdominal pain Abnormal uterine bleeding Urinary frequency Abnormal vaginal discharge Fever Decreased bowel sounds	Nucleic acid amplification tests is the best laboratory test for PID. Transvaginal utrasonography	Broad spectrum antibiotics Hospitalization
	Endometriosis	Clinical features of endometriosis include the following:^[20] Dyspareunia Nausea and vomiting Intermenstrual spotting Prolonged menstrual bleeding and increased amount of bleeding (menorrhagia) Acute abdomen	Features of iron deficiency anemia may be present such as: Low MCV, Low MCHC Elevated RBC distribution width Elevated levels of serum cancer antigen-125 in some cases.^[1] Increased levels of interleukin 1, chemoattractant protein-1 and interferon gamma may be present in patients with endometriosis. These are useful markers to monitor the disease activity and progression.^[2]	Medical therapy: Gonadotrophin releasing hormone agonists Oral contraceptive pills Aromatase inhibitors Surgery: Conservative removal of the endometrial tissues by laser or electrocautry Definitive surgeryhysterectomy with bilateral salpingo-oophorectomy.

Disease	Differentiating symptoms							Differentiating laboratory findings			Gold standard test
Disease	Hypotension	Abdominal pain	Anorexia/ weight loss	Muscle weakness	Hypoglycemia	Skin pigmentation	Other symptoms	Hyponatremia	Cortisol levels	Other labs	Gold standard test
Addison's disease	+	+	+	+	+	+		+	Low		ACTH stimulation test
Myopathies (polymyositis, hereditary myopathies)	-	-	-	+	-	Heliotrope rash and Gottron's sign	Muscle tenderness	-	Normal	-	Muscle biopsy
Celiac disease	-	+	+	-	-	Dermatitis herpetiformis	Greasy stools Increased fecal fat	-	Normal	-	Abnormal small bowel biopsy
Syndrome of inappropriate anti-diuretic hormone (SIADH)	-	-	-	-	-	-	-	+	Normal	Decreased osmolality Euvolemia Sodium in urine typically >20 mEq/L	Water deprivation test
Neurofibromatosis	-	-	+	+	-	Axillary- and inguinal-area freckling	Occasional development of peripheral sarcomas May have overgrowth of subcutaneous tissues	-	-	-	Biopsy of skin tissue
Peutz-Jeghers syndrome		+				+	Melanotic hyperpigmentation of the skin and mucous membranes	-	Normal		Colonic imaging showing the small intestinal polyps
Porphyria cutanea tarda	-	+	-	-	-	Blisters on sun-exposed sites	Associated liver disease (usually hepatitis C) Hypertrichosis	-	Normal or elevated	High level of porphyrins in the urine
Salt-depletion nephritis	+	Flank pain	-	-	-	-	Fever Dysuria Pyuria Oliguria	+	Elevated	<15:1 BUN:CR
Bronchogenic carcinoma	-	-	+	-	-	+	Cough Dyspnea Hemoptysis	-	Elevated	Increased ACTH and Hypokalemia	Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue
Anorexia nervosa	+	-	+	+	+	-	Distorted body image Oligomenorrhea	-	Elevated	-	Psychiatric condition

Disease	Clinical Findings	Laboratory findings	Management
Somatotroph adenoma: Acromegaly	Clinical features of acromegaly are due to high level of human growth hormone (hGH): Soft tissue swelling of the hands and feet Brow and lower jaw protrusion Enlarged hands Enlarged feet Arthritis and carpal tunnel syndrome Increase in teeth spacing Macroglossia (enlarged tongue) Heart failure Kidney failure Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia) Headache Diabetes mellitus Hypertension Cardiomegaly	Elevated insulin-like growth factor-1 (IGF-1) levels Elevated growth hormone levels	Medical management: Octreotide Bromocriptine Surgical management: Endonasal transsphenoidal surgery Radiation therapy
Corticotroph adenoma: Cushing's syndrome	Clinical features of Cushing's syndrome are due to increased levels of cortisol: Rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache The excess cortisol may also affect other endocrine systems and cause, for example: Insomnia Reduced libido Impotence Amenorrhea Infertility Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common.	Dexamethasone suppression test 24 hour urinary measurement of cortisol	Medical management: Pasireotide Cabergoline Ketoconazole Metyrapone Mitotane Mifepristone Surgical management: Transsphenoidal pituitary resection
Hypothyroidism	Clinical features of hypothyroidism are due to deficiency of thyroxine: Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain Hoarseness Goiter Fullness in the throat and neck Depression Emotional lability Attention deficit	Elevated TSH Low T4 Low T3 Elevated anti-thyroid antibodies(anti-TPO)	Levothyroxine
Chronic renal failure	There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include: Malaise Nausea Unintentional weight loss Pruritus Lower extremity edema Sleep disorders	Urinalysis: Albuminuria Hematuria Pyuria Red cell or white cell casts and crystals Fluid and electrolyte disturbances: Hyponatremia Hyperkalemia Hyperphosphatemia Hyperchloremia Metabolic acidosis Hypocalcemia Endocrine and metabolic disturbances: Hyperuricemia Hypertriglyceridemia Decreased HDL levels Vitamin D deficiency Increased Parathyroid hormone levels Hematologic abnormalities: Normocytic normochromic anemia Lymphocytopenia Leukopenia Thrombocytopenia	Medical management: Blood pressure management Control of blood glucose Protein restriction Management of anemia Management of electrolyte disturbance Dialysis Surgical management Kidney transplant
Liver disease: Cirrhosis	The clinical features of liver cirrhosis are very nonspecific. These include: Right upper quadrant abdominal pain Fever Fatigue and weakness Loss of appetite Diarrhea Nausea and vomiting Weight loss Abdominal pain and bloating when fluid accumulates in the abdomen Itching Menstrual irregularities	Elevated aminotransferases (AST & ALT) Elevated alkaline phosphatase (ALP) Elevated gamma-glutamyl transpeptidase Elevated bilirubin Low albumin Elevated prothrombin time Elevated globulin Hyponatremia Anemia Leukopenia and neutropenia Thrombocytopenia	Medical management: Treatment is usually directed towards the treatment of complications like ascites, esophageal varices, hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis. Some chronic constitutional symptoms that should be treated include: Pruritis: Cholestyramine is the drug of choice Hypogonadism: Topical testosterone preparations Osteoporosis: Calcium and vitamin D Pain management: NSAIDS, celecoxib, opioids Nutrition: Adequate caloric and protein intake, and multivitamin supplementation Surgical management: Liver transplantation
Seizure disorder	The clinical features of seizure disorder may include: Change in alertness, orientation and time perception Mood changes, such as unexplainable fear, panic, joy, or laughter Changes in sensation of the skin, usually spreading over the arm, leg, or trunk Vision changes, including seeing flashing lights Rarely, hallucinations (seeing things that aren't there) Falling, loss of muscle control, occurs very suddenly Muscle twitching that may spread up or down an arm or leg Muscle tension or tightening that causes twisting of the body, head, arms, or legs Shaking of the entire body Tasting a bitter or metallic flavor	Electroencephalogram	Medical management: Antiepileptic medications
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

Differentitaing hypopituitarism on the basis of GH deficiency

=== {| |- style="background: #4479BA; color: #FFFFFF; text-align: center;" ! rowspan="2" |Diseases | rowspan="2" |History and symptoms | colspan="4" |Physical Examination ! colspan="3" |Laboratory findings |- style="background: #4479BA; color: #FFFFFF; text-align: center;" !Puberty development !Height velocity !Parents height !Characteristic facies !Bone age !Genetic analysis !GH level |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Growth hormone deficiency^[22] | style="background: #F5F5F5; padding: 5px;" |

Children: delayed developmental milestones and muscle weakness
Adults: increased lean body mass, osteopenia, and dyslipidemia | style="background: #F5F5F5; padding: 5px;" |Delayed | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |
Doll-like fat distribution pattern
Immature face with under developed nasal bridge
Infantile voice | style="background: #F5F5F5; padding: 5px;" |Dlayed | style="background: #F5F5F5; padding: 5px;" |
POU1F1 gene mutations
GH1 gene mutations | style="background: #F5F5F5; padding: 5px;" |Low |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Achondroplasia^[23] | style="background: #F5F5F5; padding: 5px;" |
Normal Intelligence quotient
A trunk of average size
Arms and legs of diminished length
Spinal stenosis
Kyphosis and lordosis | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |
Large heads
Prominent forehead
Midface hypoplasia | style="background: #F5F5F5; padding: 5px;" |Delayed | style="background: #F5F5F5; padding: 5px;" | FGFR3 gene mutations | style="background: #F5F5F5; padding: 5px;" |Normal |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Familial short stature^[24] | style="background: #F5F5F5; padding: 5px;" |
A normal variant with normal signs, investigations.
Positive family history | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |Heterozygous IGF1 Splicing mutation | style="background: #F5F5F5; padding: 5px;" |Normal |- |Constitutional growth delay^[25] |
Family history of delayed growth and puberty
Childhood short stature but relatively normal adult height
Normal size at birth
A delayed growth rate begins at three to six months of age

A family history of delayed growth and puberty in one or both parents |Delayed . |Normal |Normal |Normal |Normal |Mutations in Variation in FGFR1, GNRHR, TAC3, and TACR3 genes |Normal |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Growth Hormone Resistance^[26] | style="background: #F5F5F5; padding: 5px;" |
Growth hormone insensitivity is an absence of the biological effects of growth hormone despite a normal production of GH.
Its severity correlates to IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. | style="background: #F5F5F5; padding: 5px;" |Delayed | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |
Small face in relation to head circumference
Delayed dentition | style="background: #F5F5F5; padding: 5px;" |Delayed | style="background: #F5F5F5; padding: 5px;" |
Growth hormone receptor mutations
IGF-I gene mutations | style="background: #F5F5F5; padding: 5px;" |Normal |- |Pediatric Hypothyroidism^[27] |
Low muscle tone
Cold intolerance
Persistent constipation
Fatigue and weaknessExcessive sleeping
Exaggerated jaundice |Delayed |Decreased |Normal |
Puffy facies

Macroglossia
Large fontanels
Micrognathia |Delayed | Mutations in:
Paired box 8 (PAX8)

Thyroid Transcription factor-2 (TTF2
Transcription factors NK2 |Normal |- | style="background: #DCDCDC; padding: 5px; text-align: center;" |Turner Syndrome^[28] | style="background: #F5F5F5; padding: 5px;" |
Females only
Infertility
Webbed neck
Widely spaced nipples
Broad chest
Genu valgum
Short neck
Ovarian failure | style="background: #F5F5F5; padding: 5px;" |Absent | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |Decreased | style="background: #F5F5F5; padding: 5px;" |
Low hairline
Low-set ears
Characteristic facial features | style="background: #F5F5F5; padding: 5px;" |Normal | style="background: #F5F5F5; padding: 5px;" |45 X0 | style="background: #F5F5F5; padding: 5px;" |Normal |- |Silver-Russell Syndrome^[29] |
Hemihypertrophy

Hypoglycemia
Wide fontanelle
Clinodactyly
Precocious puberty |Delayed |Decreased |Decreased |
Prominent forehead
Triangular face
Downturned corners of the mouth
Small jaw
Pointed chin |Normal | Methylation involving the H19 and IGF2 genes |Normal |- |Noonan Syndrome^[30] |
Bleeding tendency

Webbed neck

Cryptorchidism
Intellectual disability |Delayed |Decreased |Decreased |Minor facial dysmorphism |Normal |PTPN11 and SOS1 genes abnormality |Normal |- |Psychosocial Short Stature^[31] |
A disorder of short stature or growth that is observed in association with emotional deprivation
A disturbed relationship between child and caregiver is usually noted.
A history of abuse or neglect and emotional deprivation
The relationship between the caregiver and the child appears to be abnormal. |Delayed |Decreased |Normal |
Failure to thrive
Poor dental hygiene
Sad Affect |Normal |Normal |May be low |- |Short stature accompanying systemic disease^[32] |
Growth failure is seen in children with systemic diseases such as chronic kidney disease, malignancy, Chron's disease, and Cushing disease.
The primary causes of growth failure in children include metabolic acidosis, poor nutrition secondary to dietary restrictions, disturbances of growth hormone metabolism and its main mediator, insulin-like growth factor-I (IGF-I). |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 |} {| class="wikitable" !Type of DI !Subclass !Disease !Defining signs and symptoms !Lab/Imaging findings |- | rowspan="5" |Central | rowspan="3" |Acquired |Histiocytosis |
Bone lysis and fracture
Purulent otitis media
Diabetes insipidus and delayed puberty
Maxillary, mandibular, and gingival disease
Rash and maculoerythematous skin lesions
Scaly, erythematous scalp patches
Lung involvement
GI bleeding
Lymph node enlargement^[35] |
CD1a and CD45 +
Interleukin-17 (ILITA) |- |Craniopharyngioma |
Headache
Endocrine dysfunction
- Diabetes insipidus
- Hypothyroidism
- Adrenal failure
- Diabetes insipidus (eg, excessive fluid intake and urination)
- Growth failure and delayed puberty |
Suprasellar calcified cyst on MRI |- |Sarcoidosis |
Systemic complaints
- Fever
- Anorexia
- Arthralgias
Pulmonary complaints
- Dyspnea on exertion
- Cough
- Chest pain,
- Hemoptysis (rare)
Diabetes mellitus |
Hypercalcemia
Hypercalciuria (noncaseating granulomas)
Elevated alkaline phosphatase
Serum amyloid A (SAA)
ACE levels may be elevated |- | rowspan="2" |Congenital |Hydrocephalus |
Cognitive deterioration
Headaches
Neck pain
Blurred vision
Unsteady gait
Incontinence such as polyuria |Dilated ventricles on CT and MRI |- |Wolfram Syndrome (DIDMOAD) |
Diabetes Insipidus
Diabetes Mellitus
Optic Atrophy
Deafness |
Negative islet cell antibodies
Optic atrophy on electroretinogram
Deafness on audiogram
Atrophy of brain stem on MRI |- | rowspan="5" |Nephrogenic | rowspan="5" |Acquired |Drug-induced (demeclocycline, lithium) |
Polyuria
Polydipsia
Nocturia |
Urine osmolality <100 mmol/
Arginine vasopressin level >4.6 pmol/
little or no response to administration of exogenous arginine vasopressin |- |Hypercalcemia |
Polyuria
Polydipsia
Gastrointestinal disturbances
Pathological fractures
Confusion
Palpitations and cardiac arrhythmias |
Ca levels greater than 11 meq/L |- |Hypokalemia |
Polyuria
Hyporeflexia
Palpitations and cardiac arrhythmias |
K levels less than 3meq/L on CBC |- |Multiple myeloma |
Pathologic bone fractures
Bleeding
Hypercalcemia leading to polyuria
Infection
Hyperviscosity
Anemia |
IgG or IgA spike on serum protein electrophoresis
Monoclonal M spike
Disordered plasma cell proliferation on bone marrow biopsy |- |Sickle cell disease |
Chronic pain
Anemia
Aplastic crisis
Splenic sequestration
Infection
Isosthenuria presenting with polyuria |
Hemoglobin level is 5-9 g/dL
Hematocrit is decreased to 17-29%
Peripheral blood smears demonstrate target cells, elongated cells, and characteristic sickle erythrocytes
MRI can demonstrate avascular necrosis of the femoral and humeral heads |- | colspan="2" |Primary polydipsia |Psychogenic |
Polyuria
Polydipsia
Nocturia |
Dry mucus membrane
History of psychiatric disorders |- | colspan="3" |Gestational diabetes insipidus |
Polyuria
Polydipsia
Nocturia
Pregnancy |
Dry mucus membranes
Pregnancy |- | colspan="3" |Diabetes mellitus |
Polyuria
Polydipsia
Nocturia
Weight gain |
Elevated blood sugar levels >126
Elevated HbA1c > 6.5 |} ==References==

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↑ 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 <ref> tag; no text was provided for refs named pmid19949140
↑ Invalid <ref> tag; no text was provided for refs named pmid18177256
↑ Invalid <ref> tag; no text was provided for refs named pmid18415684
↑ 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.2003.09.085CS1 maint: Date and year (link)
↑ 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.

Template:WH Template:WS ===

[pmid9541295-1] Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.

[pmid7758238-2] 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.

[pmid26262437-3] 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.

[pmid7629223-4] 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.

[pmid8345854-5] 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.

[pmid21668725-6] 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.

[pmid9747750-7] 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.

[pmid19949140-8] Invalid <ref> tag; no text was provided for refs named pmid19949140

[pmid18177256-9] Invalid <ref> tag; no text was provided for refs named pmid18177256

[pmid18415684-10] Invalid <ref> tag; no text was provided for refs named pmid18415684

[fertstert2004-11] 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.2003.09.085CS1 maint: Date and year (link)

[pmid17462053-12] 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.

[pmid19679025-13] 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.

[pmid19378875-14] Trojian TH, Lishnak TS, Heiman D (2009). "Epididymitis and orchitis: an overview". Am Fam Physician. 79 (7): 583–7. PMID 19378875.

[pmid21490048-15] Stewart A, Ubee SS, Davies H (2011). "Epididymo-orchitis". BMJ. 342: d1543. PMID 21490048.

[AMN-16] 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)

[17] 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.

[pmid25992748-18] Brunham RC, Gottlieb SL, Paavonen J (2015). "Pelvic inflammatory disease". N. Engl. J. Med. 372 (21): 2039–48. doi:10.1056/NEJMra1411426. PMID 25992748.

[pmid27107781-19] Ford GW, Decker CF (2016). "Pelvic inflammatory disease". Dis Mon. 62 (8): 301–5. doi:10.1016/j.disamonth.2016.03.015. PMID 27107781.

[pmid11949938-20] Murphy AA (2002). "Clinical aspects of endometriosis". Ann N Y Acad Sci. 955: 1–10, discussion 34-6, 396–406. PMID 11949938.

[pmid21296991-21] 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.

[pmid10372687-22] 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.

[pmid26182483-23] Bouali H, Latrech H (2015). "Achondroplasia: Current Options and Future Perspective". Pediatr Endocrinol Rev. 12 (4): 388–95. PMID 26182483.

[pmid24033502-24] 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.

[pmid21292259-25] 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.

[pmid26062520-26] 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.

[pmid24662106-27] 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.

[pmid25765448-28] 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.

[pmid21349887-29] Wakeling EL (2011). "Silver-Russell syndrome". Arch Dis Child. 96 (12): 1156–61. doi:10.1136/adc.2010.190165. PMID 21349887.

[pmid17603482-30] 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.

[pmid26210627-31] 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.

[pmid24957008-32] 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.

[pmid18182313-33] 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.

[pmid26218795-34] 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.

[pmid1340034-35] 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.

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