Sheehan's syndrome 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]

Overview

Sheehan syndrome must be differentiated from lymphocytic hypophysitis, pituitary apoplexy, hypothyroidism, Addison's disease, panhypopititarism, empty sella syndrome, hypogonadotropic hypogonadism, Simmond's disease, hypoprolactinemia, menopause,female athlete triadand SAH.

Differentiating Sheehan's Syndrome from other Diseases

Sheehan's syndrome should be differentiated from other diseases causing hypopituitarism.

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
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 with key feature of traumatic delivery. -Most senitive test is 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.
Pituitary apoplexy		+/-	++	oligo/amenoorhea	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 is the initial test of choice. Pituitary hemorrhage on CT presents as a hyper-dense lesion. MRI is done in cases of inconclusive CT. An MRI is more sensitive in identifying intrasellarmass and soft tissue changes	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Lymphocytic hypophysitis		+/-	+	oligo/amenoorhea	-Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Most often seen in late pregnancy or the postpartum period Mass lesion effect such as visual field defects Hypopituitarism	-DI -Autoimmune thyroiditis	-Decreased pituitary hormones(Gonadotropins most common) -Hyperprolactinemia -GH excess	Pituitary biopsy	CT & MRI typically reveal --features of a pituitary mass -diffuse and homogeneous contrast enhancement	The most accurate test is a pituitarybiopsy which will show lymphocyticinfiltration.
Subarachnoid hemorrhage		-	-	-	Severe headache Thunderclap Described as the worst headache of life Double vision Nausea and vomiting Symptoms of meningeal irritation Sudden decreased level of consciousness	-Signs of meningeal irritation	Xanthochromia	Digital subtraction angiography	The modality of choice for diagnosis of subarachnoid hemorrhage is noncontrast head computed tomography (CT), with or without lumbar puncture.[1] CT shows hyperattenuating material filling the subarachnoid space.	Lumbar puncture (LP) is necessary when there is a strong suspicion of subarachnoid hemorrhage. LP will show: Elevated opening pressure Elevated red blood cell (RBC) Xanthochromia
Empty sella syndrome	Chronic	-	+	oligo/aenorrhea	-Erectile dysfunction -Headache -Low libido -Nipple discharge	Signs of raised intracranial pressure may be present	Decreased levels of pituitary hormones in blood.	MRI	Empty sella containing CSF
Simmond's disease/Pituitary chachexia		+/-	+	oligo/aenorrhea	-Cachexia -Premature aging	-Progressive emaciation -Loss of body hair	Decreased levels of anterior pituitary hormones in blood.
Primary Hypothyroidism		+/-	-	oligomenorrhea or menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexe	low T3,T4 High TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out ant pituitary cause
Primary Hypogonadotropic hypogonadism		-	-	oligo/aenorrhea	Hot flushes Energy and mood changes Decreased libido		Low estrogen, testosterone High FSH/LH		Done to rule out any pituitary cause	Blood tests for anemia and iron Genetic tests including a karyotype to check chromosomal structure Prolactin level (milk hormone) Sperm count Thyroid tests
Hypoprolactinemia		-	+	-	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
Panhypopituitarism		-	+	oligo/aenorrhea	Polyuria Polydipsia	-Growth failure -B/L hemianopsia -Papilledema	all pituitary hormones decreased	MRI		Left hand and wrist radiograph for bone age
Primary adrenal insufficiency		-	-	-	Hypoglycemia Hypotension	-Dehydration -Hyperpigmentation -loss of pubic and axillary hair	-Hyponatremia with/without hyperkalemia -Plasma renin activity to aldosterone ratio	CT abdomen	CT abdomen	-Serum cortisol testing -Serum ACTH testing -Antiadrenal Ab testing
Menopause
Female athlete triad

Differentiating Sheehan's syndrome on the basis of

Diseases	Course	History and Symptoms	Physical Examination	Laboratory Findings	Other Findings
							Physical Finding 1
Sheehan's Syndrome	Acute	+
Pituitary apoplexy
Lymphocytic hypophysitis
SAH
Empty sella syndrome	Chronic
Primary Hypothyroidism
Hypogonadotropic Hypogonadism
Hypoprolactinemia

Use if the above table can not be made

Differential Diagnosis	Similar Features	Differentiating Features
Differential 1	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
Differential 2	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
Differential 3	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
Differential 4	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
Differential 5	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].	On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].