A young woman with unexpected panhypopituitarism: Case Report

Abstract

Nausea and vomiting are common symptoms most frequently caused by gastrointestinal etiologies. Alternatively, panhypopituitarism is a rare condition in which two or more pituitary hormones are deficient. In this case, we describe a 25-year-old type II diabetic woman with severe and persistent nausea and vomiting. She had lost 9 kg of weight since her symptoms began 5 weeks prior. Vital signs were normal, and laboratory studies showed metabolic acidosis thought to be due to fasting ketosis. She underwent an extensive gastrointestinal workup and treatment plan without successful control or abatement of symptoms. Upon further questioning, she was found to have been experiencing secondary amenorrhea and body hair changes. Testing revealed panhypopituitarism with severe adrenocorticotropic hormone and cortisol deficiency. She was started on immediate treatment, and her symptoms resolved in less than 24 h. Imaging showed suspected Rathke’s cyst, which has since been removed. Based on similar cases and neuroanatomy, we suspect that her symptoms were due to her severe cortisol deficiency, such that a lack of sympathetic tone leads to increased vagal tone and increased neuronal signals from the brain’s emetic center. This conclusion is further supported by the rapidity of resolution of her nausea and vomiting. This case highlights this rare and severe case of panhypopituitarism and also comments on the importance of a thorough history and physical exam, which ultimately lead to the uncovering of an unexpected diagnosis.

Introduction

Nausea and vomiting are some of the most common symptoms in patients presenting to the hospital, impacting nearly all humans at some point in life. Both of these symptoms have broad differential diagnoses; but most commonly, they are caused by disorders of the upper gastrointestinal tract including viral or bacterial infection and side effects of toxins and medications. The decision for hospital admission is typically made after clinical and laboratory evaluation for vital signs and electrolyte abnormalities that necessitate treatment beyond the capabilities of a short emergency room visit. ⁴

Central causes of nausea or vomiting are rare, but potentially life-threatening, as they occur through a mechanism of increased intracranial pressure (ICP). Central nervous system tumors, cystic lesions, bleeding, and infection can all lead to increased ICP. If the ICP is able to be relieved rapidly—typically with surgery—symptoms improve rapidly. However, if ICP continues to increase, symptoms may progress to seizure, stupor, coma, and death from herniation. ¹²

Additionally, hypopituitarism is a rare, potentially fatal condition defined by the absence of one or more pituitary hormones. It may be caused by infiltration, destruction, or lack of blood supply to the pituitary. ¹⁵ Mortality in this condition is correlated with the degree of cortisol deficiency, and symptomatology is correlated to the individual hormones affected, such that thyroid stimulating hormone deficiency will cause similar symptoms to hypothyroidism and deficiencies of sex hormones may lead to secondary amenorrhea in women or loss of libido in either gender. ⁶ The goal of treatment is to replace necessary pituitary hormones to near physiologic levels to maintain homeostatic endocrine function. When determining treatment, one also must consider the developmental stage, and in reproductive-age individuals, the desire for children now and in the future. ⁷

Here, we describe a young, female patient with nausea, vomiting, and weight loss. After extensive gastrointestinal workup, symptoms persisted, and further questioning led to testing and confirmation of a diagnosis of panhypopituitarism.

Case presentation

A 25-year-old woman with 4-year history of type II diabetes mellitus presented with nausea, vomiting, and unintentional weight loss over the prior 6 weeks. Due to hypoglycemia at home, she had tapered her basal insulin from 40 to 20 units/day with continued metformin. She takes no other medications or supplements at home. A 9-kg weight loss was documented since her first emergency department visit for her symptoms just over 5 weeks prior. Her other medical history includes a Cesarean section 3 years ago after an uncomplicated pregnancy. She was followed by an endocrinologist during her pregnancy, and antibody testing confirmed a diagnosis of diabetes type II. She denied headache, blurred vision, lightheadedness, or focal weakness, and she denied alcohol, tobacco, or illicit drugs. She has a family history of diabetes and heart disease.

Vital signs were within normal ranges, including normal weight and body mass index of 23.6 kg/m². Her labs showed an anion gap metabolic acidosis with a pH of 7.203. Metabolic panel revealed a sodium of 135 mmol/L, potassium of 4.2 mmol/L, bicarbonate level of 15 mEq/L, and blood sugar of 65 mg/dL. Lactic acid was 2.7 mmol/L, and hemoglobin A1c was 5.9%. Urinalysis showed ketonuria and proteinuria. Thyroid stimulating hormone was undetectable and free thyroxine was 0.4 ng/dL (low). Pregnancy testing was negative. Computed tomography scan of the chest, abdomen, and pelvis showed mild esophageal and gall bladder thickening. The gastroenterology service was consulted and performed esophagogastroduodenoscopy with random biopsies that were normal. Gastric emptying study was attempted, but she vomited the radiopaque food.

Despite escalating treatment, symptoms were unchanged after several days. A more extensive history from the patient revealed absent menses for 6 months. She had no vaginal or nipple discharge but had noticed thinning of body hair. Given negative pregnancy testing, abnormal thyroid function, and these newly uncovered symptoms; it was highly suspected that an underlying pituitary issue was present. Additional pituitary hormones were tested, and follicle-stimulating hormone was 2.3 mIU/mL (low/normal), luteinizing hormone was 0.6 mIU/mL (low), morning cortisol was 0.23 µg/dL (very low), adrenocorticotropic hormone (ACTH) was 6.2 pg/mL (low), prolactin was 43.9 ng/mL (elevated), and insulin-like growth factor-1 was 74 ng/mL (low).

She was diagnosed with panhypopituitarism and started on corticosteroid therapy with complete symptom resolution by the next day. Magnetic resonance imaging of the brain found a T1-hyperintense lesion measuring 1.3 × 1.5 × 1.7 cm in the sella with the pituitary partially compressed and displaced. This was read as most likely representing a Rathke’s cyst, which was later confirmed during surgical resection several months later. She has tapered her corticosteroids and continues to do well.

Discussion

Hypopituitarism is a rare, potentially fatal condition, caused by damage to or external compression of the pituitary gland. Macroadenomas are the most common cause of hypopituitarism, with surgery and prior radiation therapy accounting for nearly the entire remainder of cases. Mortality rates are proportional to the degree of hypocortisolism, and females tend to have worse outcomes than males. ²

Symptomatology can vary widely, due to varying degrees of the pituitary hormones affected. The literature presents multiple case reports with varied presentations, including diabetes insipidus, adrenal crisis (with acute panhypopituitarism), pancytopenia, profound fatigue, among others. ² If sex hormones are affected or in cases of hormone-secreting tumors, such as prolactinomas, symptomatology is well-described. ² Our patient’s slight hyperprolactinemia was not consistent with prolactinoma, and is likely due to pituitary stalk interruption syndrome. ⁵

Rai et al. describe a case of a man with panhypopituitarism who presented with vertiginous syncope with nausea and vomiting that preceded his episodes. The authors reasoned that his presentation was most likely due to ACTH deficiency, because of cortisol’s role in maintaining peripheral vascular tone. ¹¹ They did not postulate a mechanism of the patient’s nausea and vomiting, but felt that it was related to increased vagal tone peri-syncopal episode. Sugi et al. present a patient with chest pain and an electrocardiogram suggestive of ST-segment elevation myocardial infarction who ultimately had panhypopituitarism. They cite additional literature reporting other cases of hypocortisolism causing musculoskeletal pain.^10,13

These cases suggest that our patient’s symptoms were also ACTH-mediated. In their review article, Heckroth et al. discuss the many neural pathways involved in the triggering of the nausea response. The “emetic center” sends its signals mainly via the vagus nerve. ⁹ Authors note multiple autonomic disorders, such as postural orthostatic tachycardia syndrome, which can be accompanied by nausea, vomiting, and abdominal pain. Multiple studies have shown that controlling the postural orthostasis and autonomic dysfunction has led to the resolution of gastrointestinal symptoms.^9,14

Additionally in our case, the speed at which our patient’s symptoms completely resolved with treatment suggests a high degree of likelihood that her symptoms were due to adrenal insufficiency. Guidelines support treatment with hydrocortisone for all patients with hypocortisolism, which is typically the most pressing and concerning feature if present. ⁴ Thyroid hormone replacement should also occur, but only after the patient has started treatment for ACTH deficiency. ⁷ Treatment should also include gonadotropin hormone replacement, which has been shown to increase positive symptom scores. ⁷ Women with intact uteri should take estrogen and progesterone to prevent endometrial hyperplasia and further treatment considerations are based on the desire for fertility in the future. ⁷ Finally, whenever panhypopituitarism is diagnosed, aggressive measures are needed to determine the underlying cause. MRI is sensitive in detecting masses, infiltrative disease, and pituitary apoplexy.^1,3

Conclusion

Panhypopituitarism is a rare, life-threatening condition due to the deficiency of multiple pituitary hormones. A thorough history and physical with serum testing for pituitary hormones can elicit the diagnosis. Although symptomatology varies, the most pressing and dangerous manifestation is ACTH deficiency. Treatment should focus on cortisol replacement, which can rapidly improve quality of life, and then investigation into the underlying cause, typically with brain MRI.