Hypogonadotrophic hypogonadism: Difference between revisions

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__NOTOC__
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{{CMG}} '''Assosciate Editor(s)-In-Chief:''' [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]]
{{CMG}}


{{SK}} Secondary hypoganadism; Central hypogonadism; gonadotropin-releasing hormone deficiency; gonadotropin deficiency
{{SK}} Secondary hypoganadism; Central hypogonadism; gonadotropin-releasing hormone deficiency; gonadotropin deficiency; HH; primary HH, secondary HH; syndromic HH; isolated hypogonadotropic hypogonadism; primary hypogonadotropic hypogonadism


==Overview==
==Overview==
'''Hypogonadotropic hypogonadism''' is a [[medical condition|condition]] which is characterized by [[hypogonadism]] due to an impaired secretion of [[gonadotropin]]s, including [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH), by the [[pituitary gland]] in the [[brain]], and in turn decreased gonadotropin levels and a resultant lack of [[sex steroid]] production.<ref name="NBK1278">{{cite web | url = http://www.ncbi.nlm.nih.gov/books/NBK1278/ | title = Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview - GeneReviews™ - NCBI Bookshelf | format = | work = | accessdate = }}</ref>
Hypogonadotropic hypogonadism is a [[medical condition|condition]] which is characterized by [[hypogonadism]] due to an impaired secretion of [[gonadotropin]]s, including [[follicle-stimulating hormone]] ([[FSH]]) and [[luteinizing hormone]] ([[LH]]), by the [[pituitary gland]] in the [[brain]], and in turn decreased gonadotropin levels and a resultant lack of [[sex steroid]] production.<ref name="NBK1278">{{cite web | url = http://www.ncbi.nlm.nih.gov/books/NBK1278/ | title = Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview - GeneReviews™ - NCBI Bookshelf | format = | work = | accessdate = }}</ref>


==Causes==
==Pathophysiology==
The type of HH, based on its cause, may be classified as either ''primary'' or ''secondary''.
The type of HH, based on its cause, may be classified as either ''primary'' or ''secondary''.
*''Primary'' HH, also called [[isolated hypogonadotropic hypogonadism|isolated HH]], is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the [[hypothalamus]] and [[anterior pituitary]]. It is caused by [[congenital disorder|congenital syndrome]]s such as [[Kallmann syndrome]] and [[gonadotropin-releasing hormone insensitivity|gonadotropin-releasing hormone (GnRH) insensitivity]].
===Primary Hypogonadotropic Hypogonadism===
*''Secondary'' HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including [[brain tumor|brain]] or [[pituitary tumor]]s, [[pituitary apoplexy]], [[head trauma]], ingestion of certain [[drug]]s, and certain [[systemic disease]]s and [[syndrome]]s.<ref name="NBK1278" />
''Primary'' HH, also called [[isolated hypogonadotropic hypogonadism|isolated HH]], is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the [[hypothalamus]] and [[anterior pituitary]]. It is caused by [[congenital disorder|congenital syndrome]]s such as [[Kallmann syndrome]] and [[gonadotropin-releasing hormone insensitivity|gonadotropin-releasing hormone (GnRH) insensitivity]].
===Secondary Hypogonadotropic Hypogonadism===
''Secondary'' HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including [[brain tumor|brain]] or [[pituitary tumor]]s, [[pituitary apoplexy]], [[head trauma]], ingestion of certain [[drug]]s, and certain [[systemic disease]]s and [[syndrome]]s.<ref name="NBK1278" />


==Diagnosis==
==Diagnosis==
===History and Symptoms===
===Symptoms===
{{See also|hypogonadism}}
Symptoms of hypogonadism include
Examples of symptoms of hypogonadism include [[delayed puberty|delayed, reduced, or absent puberty]], low [[libido]], and [[infertility]].
*[[delayed puberty|Delayed, reduced, or absent puberty]]
*Low [[libido]]
*[[Infertility]]
 
== Differentiating hypogonadism from other diseases: ==
Hypogonadotropic [[hypogonadism]] should be differentiated from other diseases causing [[hypogonadism]] like features.<ref name="pmid9541295">{{cite journal |vauthors=Sato N, Sze G, Endo K |title=Hypophysitis: endocrinologic and dynamic MR findings |journal=AJNR Am J Neuroradiol |volume=19 |issue=3 |pages=439–44 |year=1998 |pmid=9541295 |doi= |url=}}</ref><ref name="pmid7758238">{{cite journal |vauthors=Powrie JK, Powell M, Ayers AB, Lowy C, Sönksen PH |title=Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature |journal=Clin. Endocrinol. (Oxf) |volume=42 |issue=3 |pages=315–22 |year=1995 |pmid=7758238 |doi= |url=}}</ref><ref name="pmid26262437">{{cite journal |vauthors=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 |title=Diagnosis of Primary Hypophysitis in Germany |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=10 |pages=3841–9 |year=2015 |pmid=26262437 |doi=10.1210/jc.2015-2152 |url=}}</ref><ref name="pmid7629223">{{cite journal |vauthors=Thodou E, Asa SL, Kontogeorgos G, Kovacs K, Horvath E, Ezzat S |title=Clinical case seminar: lymphocytic hypophysitis: clinicopathological findings |journal=J. Clin. Endocrinol. Metab. |volume=80 |issue=8 |pages=2302–11 |year=1995 |pmid=7629223 |doi=10.1210/jcem.80.8.7629223 |url=}}</ref><ref name="pmid8345854">{{cite journal |vauthors=Imura H, Nakao K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I, Yamabe H |title=Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus |journal=N. Engl. J. Med. |volume=329 |issue=10 |pages=683–9 |year=1993 |pmid=8345854 |doi=10.1056/NEJM199309023291002 |url=}}</ref><ref name="pmid21668725">{{cite journal |vauthors=Hsieh CY, Liu BY, Yang YN, Yin WH, Young MS |title=Massive pericardial effusion with diastolic right ventricular compression secondary to hypothyroidism in a 73-year-old woman |journal=Emerg Med Australas |volume=23 |issue=3 |pages=372–5 |year=2011 |pmid=21668725 |doi=10.1111/j.1742-6723.2011.01425.x |url=}}</ref><ref name="pmid9747750">{{cite journal |vauthors=Dejager S, Gerber S, Foubert L, Turpin G |title=Sheehan's syndrome: differential diagnosis in the acute phase |journal=J. Intern. Med. |volume=244 |issue=3 |pages=261–6 |year=1998 |pmid=9747750 |doi= |url=}}</ref>
<small>
{| class="wikitable"
! rowspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diseases}}
! rowspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Onset}}
! colspan="5" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Manifestations}}
! colspan="4" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}}
|-
! colspan="4" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|History and Symptoms}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Physical examination}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Laboratory findings}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gold standard}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Imaging}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Other investigation findings}}
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Trumatic delivery}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Lactation failure}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Menstrual irregularities}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF| Other features}}
|-
![[Sheehan's syndrome]]
|Acute
|<nowiki>++</nowiki>
| ++
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Symptoms of:
* [[Adrenal insufficiency]]
 
* [[Hypothyroidism]]
|
* [[Breast tissue]] [[atrophy]]
 
* Decreased [[axillary]] and [[pubic]] hair growth
|
* [[Pancytopenia]]
 
* [[Eosinophilia]]
 
* [[Hyponatremia]]
 
* Low [[fasting plasma glucose]]
 
* Decreased levels of [[anterior pituitary]] [[hormones]] in blood
 
|
* Clinical diagnosis 
 
* Most senitive test: Low baseline [[prolactin]] levels w/o response to [[Thyrotropin-releasing hormone|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
|<nowiki>+/-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* Associated with [[autoimmune]] conditions
 
* Generalized [[headache]]
 
* Retro-orbital or Bitemporal [[pain]]
 
* Mass lesion effect such as [[Visual field defect|visual field defects]]
|
* [[Diabetes insipidus|DI]]
 
* [[Autoimmune]] [[thyroiditis]]
|
* Decreased pituitary hormones([[Gonadotropins]] most common)
 
* [[Hyperprolactinemia]](40%)
 
* [[Growth hormone|GH]] excess
|
* [[Pituitary gland|Pituitary]] [[biopsy]]: [[lymphocytic]] [[Infiltration (medical)|infiltration]]
|
* [[CT]] & [[MRI]]: Features of a [[Pituitary gland|pituitary]] [[mass]]
 
* Diffuse and homogeneous contrast enhancement
|[[Assay|Assays]] for:
* Anti-TPO 
* Anti-Tg Ab
|-
![[Pituitary apoplexy]]
|Acute
|<nowiki>+/-</nowiki>
|<nowiki>++</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|Severe [[headache]]
* [[Nausea and vomiting]]
* Paralysis of eye muscles ([[diplopia]])
* Changes in vision
|
* [[Visual acuity]] defects
 
* [[Cranial nerve palsies|CN palsies]] (nerves III, IV, V , and VI)
 
|
* Decreased levels of [[anterior]] pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* [[CT]] scan without [[Contrast medium|contrast]]: Hemorrhag<nowiki/>e on [[CT]] presents as a hyperdense lesion
 
* [[MRI]]: If inconclusive [[CT]]
|
[[Blood tests]] may be done to check:
* [[PT]]/[[INR]] and [[aPTT]]
 
* [[Pituitary gland|Pituitary]] [[hormonal]] assay
|-
![[Empty sella syndrome]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Erectile dysfunction]]
 
* [[Headache]]
 
* Low [[libido]]
 
|
* Signs of raised [[intracranial pressure]] may be present
 
* [[Nipple discharge|Nipple]] discharge
|
* Decreased levels of  pituitary hormones in blood.
|
* [[MRI]]
|
* [[Empty sella]] containing [[Cerebrospinal fluid|CSF]]
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
![[Simmond's Disease|Simmonds' disease]]/[[Pituitary]] [[cachexia]]
|Chronic
|<nowiki>+/-</nowiki>
| +
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Cachexia]]
* [[Premature aging|Premature]] aging
|
* Progressive [[emaciation]]
 
* Loss of body hair
|
* Decreased levels of anterior pituitary hormones in blood.
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Pituitary hormone stimulation tests ([[Metoclopramide]] and [[clomiphene citrate]] stimulation tests)
|-
! [[Primary hypothyroidism|Hypothyroidism]]
|Chronic
|<nowiki>+/-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea]]/[[menorrhagia]]
|
* Cold intolerance
* [[Constipation]]
|
* Dry skin
 
* [[Bradycardia]]
 
* Hair loss
 
* [[Myxedema]]
 
* Delayed relaxation phase of deep [[Tendon reflex|tendon reflexes]]
|
* Low [[T3]],[[T4]]
 
* Normal/ low [[Thyroid-stimulating hormone|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
|-
![[Hypogonadotropic hypogonadism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flushes]]
 
* Energy and mood changes
 
* Decreased [[libido]]
|
* [[Breast tissue]] [[atrophy]]
* Decreased [[maturation]] of [[vaginal]] [[mucosa]]
|
* Low [[estrogen]], [[testosterone]]
 
* High [[FSH]]/[[Luteinizing hormone|LH]]
|
* [[FSH]]
* [[Luteinizing hormone|LH]]
|
* Done to rule out any pituitary cause
|
* Genetic tests  ([[karyotype]])
* Measurement of total and free [[testosterone]] and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] concentrations
|-
!Hypoprolactinemia
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
* [[Infertility]]
* Subfertiliy
|
* Puerperal agalactogenesis
|
* No workup is necessary
|
* Decreased prolactin levels
|
* Done to rule out any pituitary cause
|
* [[Prolactin]] assay in [[3rd trimester]]
 
* [[Luteinizing hormone|LH]], [[Follicle-stimulating hormone|FSH]]
 
* [[Thyrotropin]] and free [[thyroxine]]
|-
![[Panhypopituitarism]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Polyuria]]
 
* [[Polydipsia]]
* Features of [[hypothyroidism]] and [[hypoadrenalism]]
|
* [[Growth failure]]
 
* B/L [[hemianopsia]]
 
* [[Papilledema]]
|
* All pituitary hormones decreased
|
* [[Magnetic resonance imaging|MRI]]
|
* Done to rule out any pituitary cause
|
* Left hand and wrist [[radiograph]] for [[bone age]]
|-
![[Primary adrenal insufficiency]]/[[Addison's disease]]
|Chronic
|<nowiki>-</nowiki>
| -
|<nowiki>-</nowiki>
|
* [[Hypoglycemia]]
 
* [[Hypotension]]
|
* [[Dehydration]]
 
* [[Hyperpigmentation]]
 
* loss of [[pubic]] and [[axillary]] hair
 
|
* [[Hyponatremia]] with/without [[hyperkalemia]]
 
* [[Plasma renin activity]] to [[Aldosterone|aldosterone ratio]]
|
* Abdominal [[Computed tomography|CT]]
|
* Abdominal [[Computed tomography|CT]]
|
* Serum [[cortisol]] testing
 
* Serum [[ACTH]] testing
 
* Anti-adrenal [[Antibody|Ab]] testing
|-
![[Menopause]]
|Chronic
|<nowiki>-</nowiki>
|<nowiki>+/-</nowiki>
|[[Oligomenorrhea|Oligo]]/[[amenorrhea]]
|
* [[Hot flashes]]
* [[Insomnia]]
* [[Weight gain]] and [[bloating]]
* Mood changes
|
* [[Vaginal atrophy]]
* Loss of pelvic [[muscle tone]]
|
* ↑ [[FSH]]
* ↓ [[Estradiol]] and [[inhibin]]
|
* [[FSH]] > [[LH]]
|Normal
|
* [[Endometrial biopsy]]
|}
<small>


==Treatment==
==Treatment==
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{{Reflist|2}}
{{Reflist|2}}


[[Category:Disease]]
[[Category:Endocrinology]]
[[Category:Pediatrics]]
{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Disease]]

Latest revision as of 19:44, 14 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S

Synonyms and keywords: Secondary hypoganadism; Central hypogonadism; gonadotropin-releasing hormone deficiency; gonadotropin deficiency; HH; primary HH, secondary HH; syndromic HH; isolated hypogonadotropic hypogonadism; primary hypogonadotropic hypogonadism

Overview

Hypogonadotropic hypogonadism is a condition which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.[1]

Pathophysiology

The type of HH, based on its cause, may be classified as either primary or secondary.

Primary Hypogonadotropic Hypogonadism

Primary HH, also called isolated HH, is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the hypothalamus and anterior pituitary. It is caused by congenital syndromes such as Kallmann syndrome and gonadotropin-releasing hormone (GnRH) insensitivity.

Secondary Hypogonadotropic Hypogonadism

Secondary HH, also known as acquired or syndromic HH, is far more common than primary HH, and is responsible for most cases of the condition. It has a multitude of different causes, including brain or pituitary tumors, pituitary apoplexy, head trauma, ingestion of certain drugs, and certain systemic diseases and syndromes.[1]

Diagnosis

Symptoms

Symptoms of hypogonadism include

Differentiating hypogonadism from other diseases:

Hypogonadotropic hypogonadism should be differentiated from other diseases causing hypogonadism like features.[2][3][4][5][6][7][8]

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 Symptoms of:
  • Clinical diagnosis
  • 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
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.
Simmonds' disease/Pituitary cachexia Chronic +/- + Oligo/amenorrhea
  • Loss of body hair
  • Decreased levels of anterior pituitary hormones in blood.
  • Done to rule out any pituitary cause
Hypothyroidism Chronic +/- - Oligomenorrhea/menorrhagia
  • Dry skin
  • Hair loss
  • Normal/ low TSH
  • Rest of pituitary hormone levels WNL
  • Done to rule out any pituitary cause
  • Assays for anti-TPO and anti-Tg Ab
  • FNA biopsy
Hypogonadotropic hypogonadism Chronic - - Oligo/amenorrhea
  • Energy and mood changes
  • Done to rule out any pituitary cause
Hypoprolactinemia Chronic - + -
  • Puerperal agalactogenesis
  • No workup is necessary
  • Decreased prolactin levels
  • Done to rule out any pituitary cause
Panhypopituitarism Chronic - + Oligo/amenorrhea
  • All pituitary hormones decreased
  • Done to rule out any pituitary cause
Primary adrenal insufficiency/Addison's disease Chronic - - -
  • Abdominal CT
  • Abdominal CT
  • Anti-adrenal Ab testing
Menopause Chronic - +/- Oligo/amenorrhea Normal

Treatment

Treatment of HH may consist of administration of either a GnRH agonist or a gonadotropin formulation in the case of primary HH and treatment of the root cause (e.g., a tumor) of the symptoms in the case of secondary HH. Alternatively, hormone replacement therapy with androgens and estrogens in males and females, respectively, may be employed.

See also

References

  1. ↑ 1.0 1.1 "Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency Overview - GeneReviews™ - NCBI Bookshelf".
  2. ↑ Sato N, Sze G, Endo K (1998). "Hypophysitis: endocrinologic and dynamic MR findings". AJNR Am J Neuroradiol. 19 (3): 439–44. PMID 9541295.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.

Template:WH Template:WS

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