Hypopituitarism differential diagnosis

Hypopituitarism Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Hypopituitarism from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Hypopituitarism differential diagnosis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Hypopituitarism differential diagnosis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Hypopituitarism differential diagnosis
CDC on Hypopituitarism differential diagnosis
Hypopituitarism differential diagnosis in the news
Blogs on Hypopituitarism differential diagnosis
Directions to Hospitals Treating Hypopituitarism
Risk calculators and risk factors for Hypopituitarism differential diagnosis

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 should be differentiated from other diseases causing panhypopituitarism, hypothyroidism, hypogonadism, ACTH deficiency, GH deficiency, ADH deficiency and high prolactin level.

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 gonadotropins (FSH/LH) deficiency, click here.
• For the differential of hypopituitarism on the basis of ACTH deficiency, click here.
• For the differential of hypopituitarism on the basis of high prolactin level, click here.
• For the differential of hypopituitarism on the basis of growth hormone deficiency, click here.
• For the differential of hypopituitarism on the basis of ADH deficiency, click here.

Differentiating various causes of Panhypopituitarism

Hypopituitarism should be differentiated from other diseases causing panhypopituitarism, hypothyroidism, hypogonadism, ACTH deficiency, GH deficiency, ADH deficiency and high prolactin level.

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	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 sensitive 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)

Differentiating hypopituitarism from hypothyroidism that present as a single hormonal deficiency

Disease		History and symptoms			Laboratory findings							Additional findings
		Fever	Goiter	Pain	TSH	Free T4	T3	T3RU	Thyroglobin	TRH	TPOAb
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
	Hypothalamus	+	-	-				↑	Normal	↓	Normal	Other pituitary hormone deficiencies signs
Resistance to TSH/TRH		-	-	-	↑	N/↓	N/↓	Normal	Normal	↑/↓	Normal	Rare

Differentiating hypopituitarism on the basis of Gonadotropins (FSH/LH) deficiency

Diseases		Clinical findings	Diagnosis	Manangement
Congenital diseases	Klinefelter syndrome	Clinical features of Klinefelter syndrome are as the following: 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: 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 undescended testes.
Male diseases	Testicular torsion	Patients of testicular torsion usually present with following: Sudden onset of severe pain in one testicle, with or without a previous predisposing event Swelling on 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.
	Orchitis	Clincial features of orchitis include the following: 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 infection.
Female diseases	Polycystic ovarian syndrome (PCOS)	Possible clinical findings in cases of PCOS: Amenorrhea Oligomenorrhea Ovarian cysts Pelvic pain Dyspareunia Acne Hirsutism Anxiety and depression Sleep apnea	Blood testosterone level LH and FSH levels Pelvic ultrasound	Clomiphene citrate and metformin to manage infertility. Cyproterone acetate for the treatment of acne and hirsutism. Spironolactone
	Pelvic inflammatory disease	Patients usually present with the following: Bilateral abdominal pain Abnormal uterine bleeding Urinary frequency Abnormal vaginal discharge Fever Decreased bowel sounds	Nucleic acid amplification test is the best laboratory test for PID. Transvaginal ultrasonography	Broad spectrum antibiotics Hospitalization
	Endometriosis	Clinical features of endometriosis include the following: 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: Gonadotropin releasing hormone agonists Oral contraceptive pills Aromatase inhibitors Surgery: Conservative removal of the endometrial tissues by laser or electrocautery Definitive surgery hysterectomy with bilateral salpingo-oophorectomy.

Differentiating hypopituitarism on the basis of ACTH Deficiency

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 (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

Differentiating hypopituitarism on the basis of High prolactin level

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	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	Children: delayed developmental milestones and muscle weakness Adults: increased lean body mass, osteopenia, and dyslipidemia	Delayed	Decreased	Normal	Doll-like fat distribution pattern Immature face with under developed nasal bridge Infantile voice	Dlayed	POU1F1 gene mutations  GH1 gene mutations	Low
Achondroplasia	Normal Intelligence quotient A trunk of average size Arms and legs of diminished length Spinal stenosis Kyphosis and lordosis	Normal	Decreased	Decreased	Large heads Prominent forehead Midface hypoplasia	Delayed	FGFR3 gene mutations	Normal
Familial short stature	A normal variant with normal signs, investigations Positive family history	Normal	Decreased	Decreased	Normal	Normal	Heterozygous IGF1 Splicing mutation	Normal
Constitutional growth delay	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
Growth Hormone Resistance	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.	Delayed	Decreased	Normal	Small face in relation to head circumference Delayed dentition	Delayed	Growth hormone receptor mutations IGF-I gene mutations	Normal
Pediatric Hypothyroidism	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
Turner Syndrome	Females only Infertility Webbed neck Widely spaced nipples Broad chest Genu valgum Short neck Ovarian failure	Absent	Decreased	Decreased	Low hairline Low-set ears Characteristic facial features	Normal	45 X0	Normal
Silver-Russell Syndrome	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	Bleeding tendency Webbed neck Cryptorchidism Intellectual disability	Delayed	Decreased	Decreased	Minor facial dysmorphism	Normal	PTPN11 and SOS1 genes abnormality	Normal
Psychosocial Short Stature	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	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	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	Normal

Differentiating hypopituitarism on the basis of ADH deficiency

Type of DI	Subclass	Disease	Defining signs and symptoms	Lab/Imaging findings
Central	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	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
	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
Nephrogenic	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
Primary polydipsia		Psychogenic	Polyuria Polydipsia Nocturia	Dry mucus membrane History of psychiatric disorders
Gestational diabetes insipidus			Polyuria Polydipsia Nocturia Pregnancy	Dry mucus membranes Pregnancy
Diabetes mellitus			Polyuria Polydipsia Nocturia Weight gain	Elevated blood sugar levels >126 Elevated HbA1c > 6.5

References