EM@3AM: Panhypopituitarism – emDocs

A 40-year-old female presents to the ED obtunded and diaphoretic. She is accompanied by her husband. Point of care (POC) glucose reveals a blood sugar of 40 mg/dL. An amp of D50 is ordered and collateral history is obtained from the husband. He states that the patient has felt nauseous for the past 24 hours and has had multiple episodes of non-bloody, non-bilious emesis. She has not had any fever, diarrhea, or abdominal pain. No sick contacts at home. Over the past year the patient has been experiencing increased fatigue and weight gain. She recently saw her PCP for chronic headaches, which she has been managing with over-the-counter analgesics. The patient does not take any medications.

Initial vital signs include temperature 37.0 C, BP 85/60 mmHg HR 110 bpm, RR 12, SpO2 97% on room air. Patient is diaphoretic but has improved mentation after the D50 bolus. Repeat glucose is 70 mg/dL. Some thinning hair and cracked nails are noted on exam. She has tachycardic with no murmurs, rubs, or gallops. Lungs are clear to auscultation bilaterally. Abdomen is soft and nontender. She has trace symmetric bilateral pedal edema. She is AOx4, and no focal neurologic deficits are notes.

IV fluids are ordered, and POC Chem-7 shows Na of 128 and K of 3.8. Despite appropriate fluid resuscitation, the patient remains hypotensive and has a repeat episodes of hypoglycemia.

Question: What is the diagnosis?

Answer: Panhypopituitarism

 Background:

• Broad etiology ranging from acute to chronic presentations. Sometimes a physiologic stressor can cause acute transition of previously chronic course.¹
• Though all pituitary hormones can be affected, the emergent presentation is usually mediated by hypocortisolism and hypothyroidism.¹
• Differs from primary adrenal insufficiency in that aldosterone is unaffected, and thus potassium is typically normal. Sodium can be either low or normal.¹

Etiology:²

• Non tumoral causes (50%)
  • Pituitary apoplexy (sudden hemorrhage)
    • Most commonly occurring in pituitary adenomas. Can also occur in the setting of microadenomas, or Rathke cleft cysts.¹⁵
  • Pituitary infarction (Sheehan’s Syndrome) à infarction of the pituitary gland after postpartum hemorrhage
  • Traumatic brain injury
  • Infection
  • Stroke (ischemic, subarachnoid hemorrhage)
  • Radiation
  • Infiltrative (hemochromatosis, sarcoidosis)
  • Autoimmune/inflammatory (Lymphocytic hypophysitis, complication of immunotherapy)
• Tumors (pituitary adenoma, craniopharyngioma) (50%)

Epidemiology:

• Given the broad etiology, there is no uniform epidemiology.
• In children, it is more commonly congenital.
• Can occur at any age.²

Clinical Presentation:

• Panhypopituitarism causes secondary adrenal insufficiency
  • Secondary adrenal insufficiency does not present with hyperpigmentation of the skin³ as opposed to primary adrenal insufficiency.
• Clinical presentation is also broad, though hallmark features are based upon the deficient hormones.
  • Even in panhypopituitarism which affects all pituitary hormones it can be partial or complete deficiency.

• Usually, the presenting emergent symptoms result from deficiencies of corticotropin (ACTH), and thyroid-stimulating hormone (TSH).¹
  • ACTH deficiency¹
    • Hypotension, confusion, hypoglycemia
  • TSH deficiency¹
    • Bradycardia, hypothermia, constipation, weight gain
  • Other pituitary hormones
    • Follicle-stimulating hormone (FSH)

• Amenorrhea, decreased spermatogenesis, decreased libido, hot flashes¹

• • • Growth hormone (GH)
      • Short stature in children. Increased fat and decreased lean body mass in adults.
    • Prolactin
      • Inability to lactate after delivery

Diagnosis:

• Definitive diagnosis typically occurs outside of the ED with results from initial labs, 24-hour cortisol, ACTH stimulation test, and possibly abdominal imaging if there is clinical concern for primary adrenal insufficiency.^3,4
• The relevant question in the ED is if the patient has a primary vs. secondary etiology of adrenal insufficiency, and if there is concurrent hypothyroidism, or other features to suggest panhypopituitarism.

Initial Evaluation/Stabilization:

• Isotonic fluids – NS favored over LR¹ due to theoretical risk of LR worsening hyponatremia, though data supporting this are limited.
• IV glucocorticoid therapy if suspecting this diagnosis.
• BMP, POC glucose, TSH, free T4
• If no established diagnosis of adrenal insufficiency:
  • Order cortisol, corticotropin (ACTH), aldosterone, renin.
  • Preferably obtain labs before giving glucocorticoids, but diagnostics should not delay emergency management.
• Consider head imaging for relevant diagnoses
  • Pituitary apoplexy, pituitary adenoma, craniopharyngioma, Sheehan syndrome, stroke
    • Initial evaluation with CT head, +/- CTA head and neck +/- CSF studies if onset >6hrs for thunderclap headache due to the concern of subarachnoid hemorrhage (SAH). MRI has greater sensitivity for diagnosing small tumors and may be indicated based on clinical judgement if initial imaging is non-diagnostic.^5,6

Treatment:

• Initial therapy with steroids. Typically tapered over 3 days.

• • Electrolyte management¹
    • Cortisol deficiency can cause hypoglycemia and hyponatremia. Hyperkalemia suggests mineralocorticoid deficiency.
    • Hyponatremia
      • Repletion with isotonic fluids with Q2-6H BMPs. Glucocorticoid therapy and isotonic repletion should correct hyponatremia.
      • Careful attention needs to be given to avoid rapid correction of sodium and cause osmotic demyelination.
      • Investigate other causes if hyponatremia fails to resolve with treatment.
    • Hypoglycemia
      • Dextrose boluses as needed for blood glucose 55 mg/dL or less.
      • Maintenance with D5 w/0.9% NS. Be aware that glucocorticoid therapy could result in hyperglycemia.
      • 4 mL / kg / hour for the first 10kg of body mass, 2 mL / kg / hour for the second 10kg of body mass (11kg – 20kg), 1 mL / kg / hour for any kilogram of body mass above 20kg (> 20kg).
      • 110cc/hr for a 70 kg adult.

• • • Hyperkalemia
      • Membrane stabilization, shifting agents, potassium removal if EKG changes.
        • Calcium
        • Albuterol
        • Dextrose/insulin
        • Dialysis/gastrointestinal cation exchangers/diuretics
      • If caused by mineralocorticoid deficiency, it should correct within a few hours of mineralocorticoid treatment. If it does not, evaluate for other causes.
  • Hypothyroidism^13,14
    • Administer levothyroxine if evidence of hypothyroidism
      • Approximate starting dose is 1.6 mcg/kg body weight per day. Notably the range can vary significantly, and requires subsequent titration
• Disposition: Hospital vs ICU admission depending on clinical presentation. Consider endocrine consultation, and neurosurgical consultation if concern for intracranial hemorrhage

Pearls:

• The emergent presentation of panhypopituitarism is usually characterized by signs and symptoms of adrenal insufficiency and hypothyroidism.
• There is a broad etiology for panhypopituitarism that can present either acutely or as acute transition of chronic symptoms due to physiologic stress.
• The presentation of primary and secondary adrenal insufficiency are very similar, initially differentiated with the presence or absence of hyperkalemia. Consider mineralocorticoid coverage if there is clinical concern for primary adrenal insufficiency.

A 27-year-old woman presents to the ED with fatigue, malaise, and weakness. She states she has felt exhausted since the birth of her son. She does not enjoy the things she previously enjoyed and has no energy to care for herself or her son. She has been unable to breastfeed successfully and has had to feed her son formula as a result. Prior to her pregnancy, she had regular menses but has not yet resumed her menstrual cycles. She has no known medical conditions. Her T is 96°F (35.6°C), BP is 92/61 mm Hg, HR is 120 bpm, RR is 16/min, and SpO2 is 100% on room air. Physical exam reveals a fatigued woman with a depressed affect. Laboratory studies are notable for a sodium of 120 mEq/L. Which of the following is the most likely etiology of this patient’s symptoms?

A) Autoimmune adrenal injury

B) Hemorrhage during delivery

C) Increased antidiuretic hormone release

D) Postpartum depression

Correct answer: B

This patient’s symptoms, including fatigue, malaise, persistent weakness, inability to breastfeed, amenorrhea, and hypotension, are most consistent with Sheehan syndrome, a condition caused by pituitary infarction due to postpartum hemorrhage. During pregnancy, the pituitary gland enlarges due to increased lactotroph stimulation. If significant blood loss occurs during delivery, the pituitary becomes vulnerable to ischemic necrosis due to its increased metabolic demand and relatively low blood supply. The resulting hypopituitarism leads to deficiencies in multiple anterior pituitary hormones, including prolactin, gonadotropins, adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH), which contribute to this patient’s inability to breastfeed, amenorrhea, hypotension, and fatigue.

One of the key features of Sheehan syndrome is secondary adrenal insufficiency, which results from a deficiency in ACTH. Unlike primary adrenal insufficiency, in which both cortisol and aldosterone are deficient, aldosterone remains intact in secondary adrenal insufficiency because the renin-angiotensin-aldosterone system, rather than ACTH, regulates it. As a result, patients do not develop hyperkalemia but may have hyponatremia due to cortisol deficiency and inappropriate antidiuretic hormone (ADH) secretion, leading to free water retention and dilutional hyponatremia. This explains the patient’s low sodium levels (120 mEq/L) and hypotension, which is further exacerbated by cortisol deficiency.

The patient’s inability to breastfeed is due to prolactin deficiency, as the pituitary normally secretes prolactin to stimulate lactation. The absence of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) contributes to persistent amenorrhea, as ovarian estrogen and progesterone production fail to resume postpartum. The deficiency of TSH can lead to hypothyroidism, further exacerbating the patient’s fatigue and depressed affect, which can sometimes be mistaken for postpartum depression.

Autoimmune adrenal injury (A) would cause primary adrenal insufficiency, which results from direct damage to the adrenal glands, often due to autoimmune destruction (e.g., autoimmune adrenalitis, part of a polyglandular autoimmune syndrome). In primary adrenal insufficiency, both cortisol and aldosterone are deficient, leading to severe hypotension, fatigue, weight loss, hyperpigmentation, hyponatremia, and hyperkalemia. This patient has fatigue and hyponatremia, but she lacks hyperkalemia and hyperpigmentation, both of which are characteristic of primary adrenal insufficiency. Additionally, autoimmune adrenal insufficiency does not explain her inability to breastfeed or amenorrhea, which suggests a pituitary disorder rather than adrenal gland dysfunction.

Syndrome of inappropriate ADH secretion (SIADH) (C) is a disorder that causes hyponatremia due to excessive free water retention, leading to euvolemic hyponatremia. While SIADH can present with fatigue, weakness, and low sodium levels, it does not cause hypotension, as total body sodium and volume remain normal. More importantly, SIADH would not explain amenorrhea or inability to breastfeed, as ADH does not affect gonadotropins (LH, FSH) or prolactin. The patient’s history of postpartum hemorrhage suggests pituitary dysfunction (Sheehan syndrome) rather than SIADH.

Postpartum depression (D) can cause fatigue, anhedonia, and low energy, which overlap with this patient’s symptoms. However, it does not explain her hypotension, hyponatremia, inability to lactate, or amenorrhea, which are suggestive of an endocrine disorder rather than a purely psychological one. Additionally, postpartum depression does not cause low cortisol, ACTH, or thyroid hormone levels, which are responsible for the patient’s profound fatigue and hypotension. This patient’s symptoms are hormonal in nature, not psychiatric, ruling out postpartum depression as the cause.

Rosh Review Website Link

References:

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