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]


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

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.[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
  • All pituitary hormones decreased
Sheehan's syndrome Acute ++ ++ Oligo/amenorrhea
  • Dx is clinical
  • Most sensitive test: low baseline prolactin levels w/o response to TRH
  • Sequential changes of pituitary enlargement followed by
  • Shrinkage and necrosis leading to decreased sellar volume or empty sella
Lymphocytic hypophysitis Acute +/- + Oligo/amenorrhea
  • Retro-orbital or Bitemporal pain
  • Diffuse and homogeneous contrast enhancement
Assays for:
  • Anti-TPO
  • Anti-Tg Ab
Pituitary apoplexy Acute +/- ++ Oligo/amenorrhea Severe headache
  • Decreased levels of anterior pituitary hormones in blood.
  • CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion

Blood tests may be done to check:

Empty sella syndrome Chronic - + Oligo/amenorrhea
  • Decreased levels of pituitary hormones in blood.
Simmond's disease/Pituitary cachexia Chronic +/- + Oligo/amenorrhea
  • Loss of body hair
  • Decreased levels of anterior pituitary hormones in blood.

Differentiating hypopituitarism from hypothyroidism that present as a single hormonal deficiency

[8] [9][10][11]

Disease History and symptoms Laboratory findings Additional findings
Fever Goiter Pain TSH Free T4 T3 T3RU Thyroglobin TRH TPOAb
Primary hypothyroidism Autoimmune + +/-


- 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/
  • Asymptomatic
Central Hypothyroidism Pituitary + - - N/ N/ N/ Normal Normal Normal
Hypothalamus + - - Normal Normal
Resistance to TSH/TRH - - - N/ N/ Normal Normal / Normal
  • Rare

Legend:'TSH: Thyroid stimulating hormone, T4: Teraiodothyronine, T3: Triiodothyronine, T3RU: Triiodothyronine reuptake, TRH: Thyrotrophin releasing hormone, TPOAb: Thyroid peroxidase antibody, N: Normal, +: Present, -: Absent

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:[12]
  • Language learning impairment.
Kallmann syndrome Clinical features of Kallmann syndrome include:

Differentiating hypopituitarism on the basis of High prolactin level


Disease Clinical Findings Laboratory findings Management
Somatotroph adenoma:


Clinical features of acromegaly are due to high level of human growth hormone (hGH):
Corticotroph adenoma: Cushing's syndrome Clinical features of Cushing's syndrome are due to increased levels of cortisol:
Hypothyroidism Clinical features of hypothyroidism are due to deficiency of thyroxine:
  • Fullness in the throat and neck
Chronic renal failure There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include: Urinalysis:

Fluid and electrolyte disturbances:

Endocrine and metabolic disturbances:

Hematologic abnormalities:

Liver disease: Cirrhosis The clinical features of liver cirrhosis are very nonspecific. These include:
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
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[31] 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[32] Delayed Decreased Normal
  • Doll-like fat distribution pattern
  • Immature face with under developed nasal bridge
  • Infantile voice
  • POU1F1 gene mutations 
  • GH1 gene mutations
Achondroplasia[33] Normal Decreased Decreased
  • Large heads
  • Prominent forehead
  • Midface hypoplasia

FGFR3 gene mutations

Familial short stature[34]
  • A normal variant with normal signs, investigations
  • Positive family history
Normal Decreased Decreased Normal Normal Heterozygous IGF1 Splicing mutation Normal
Constitutional growth delay[35]
  • 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 FGFR1GNRHR, TAC3, and TACR3 genes Normal
Growth Hormone Resistance[36] Delayed Decreased Normal
  • Small face in relation to head circumference
  • Delayed dentition
Delayed Normal
Pediatric Hypothyroidism[37] Delayed Decreased Normal
  • Puffy facies

Mutations in:

  • Thyroid Transcription factor-2 (TTF2
  • Transcription factors NK2
Turner Syndrome[38] Absent Decreased Decreased Normal 45 X0 Normal
Silver-Russell Syndrome[39] 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[40] Delayed Decreased Decreased Minor facial dysmorphism Normal PTPN11 and SOS1 genes abnormality Normal
Psychosocial Short Stature[41]
  • 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 Normal Normal May be low
Short stature accompanying systemic disease[42] Delayed Decreased Normal Failure to thrive Delayed Normal Normal
Idiopathic short stature[43] 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[44] Normal

Differentiating hypopituitarism on the basis of ADH deficiency

Type of DI Subclass Disease Defining signs and symptoms Lab/Imaging findings
Central Acquired Histiocytosis
  • CD1a and CD45 +
  • Interleukin-17 (ILITA)
Congenital Hydrocephalus Dilated ventricles on CT and MRI
Wolfram Syndrome (DIDMOAD)
Nephrogenic Acquired Drug-induced (demeclocycline, lithium)
  • Ca levels greater than 11 meq/L
  • K levels less than 3meq/L on CBC
Multiple myeloma
Sickle cell disease
Primary polydipsia Psychogenic
Gestational diabetes insipidus
Diabetes mellitus
  • Elevated blood sugar levels >126
  • Elevated HbA1c > 6.5

Hypopituitarism must be differentiated from other causes of headache, polyuria and polydypsia.

Disease Causes Symptoms Diagnosis and treatment
SIADH SIADH is a syndrome characterized by excessive release of antidiuretic hormone (ADH or vasopressin) from the posterior pituitary gland or another source. The result is hyponatremia, and sometimes fluid overload
  • Urine sodium concentration>40mmol/litre
Cerebral salt wasting syndrome Cerebral salt wasting syndrome is defined as therenal loss of sodium during intracranial disease leading to hyponatremia and a decrease in extracellular fluid volume The patient is Treatment is
Adrenal insufficiency Adrenal insufficiency

Adrenal insufficiency can be

Common causes of primary adrenal insufficiency:

Chronic disease is characterized by

Acute addisonian crisis is characterized by:

The diagnosis of Addisons disease is made through rapid ACTH administration and measurement of cortisol.

The definitive diagnosis is the cosyntropin or ACTH stimulation test. Acortisol level is obtained before and after administering ACTH. A normal person should show a brisk rise in cortisol level after ACTH administration.

Management: The management of Addison disease involves:

Adrenal crisis:

Hypopituitarism Abnormality in anterior pituitary function

Etiology is as follows:

Signs and symptoms ofhypopituitarism vary, depending on the deficient

hormone and severity of the disorder,some of the symptoms may be as follows:

The treatment of permanent hypopituitarism consists of replacement of the peripheral hormones

Hypothyroidism Hypofunctioning of the thyroid gland due to multifactorial etiology ranging from congenital to autoimmune causes described below: Diagnosis of hypothyroidism is based on blood tests:
Psychogenic polydipsia Also called as primary polydipsia is characterized bypolyuria and polydipsia. Causes are: Evaluation ofpsychiatric patients with polydipsia requires an evaluation for other medical causes of polydipsia, polyuria,hyponatremia, and the syndrome of inappropriate secretion of antidiuretic hormone.
  • The management strategy inpsychiatric patients should include:



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