Pituitary microadenoma with hypopituitarism presenting as hyponatremia

Abstract

The incidence of pituitary adenoma has been increasing these days. Majority of the cases are incidental findings on imaging; and these patients may be asymptomatic without any laboratory abnormalities. However, a non-functional sellar mass can initially present with hypopituitarism. The patient being described is an elderly female who presented with severe hyponatraemia. She has history of recurrent admissions for hyponatraemia in the past. Her biochemical evaluation revealed hypopituitarism and magnetic resonance imaging of brain showed pituitary microadenoma. Hyponatraemia as a presenting feature of hypopituitarism due to pituitary microadenoma is an uncommon scenario.

Background

Pituitary adenomas are a group of tumours that arise from the pituitary gland; and can be functional (hormone-producing) or non-functional (non-hormone producing). These tumours, due to their mass effect and aberrant hormonal production, are associated with increased morbidity and mortality.¹ Pituitary adenomas are classified, based on their size, as microadenomas (diameter <1 cm) and macroadenomas (diameter >1 cm).^{2 3} With increased use of imaging modalities like CT and MRI, the number of incidentally detected pituitary masses have increased. Though microadenomas are more common, the exact prevalence is difficult to measure as majority of these adenomas exist without any clinical symptoms.^1–3

Case presentation

A 70-year-old woman was brought to the emergency department with fatigue and repeated episodes of non-projectile vomiting with nausea. There was no history of fever or trauma. She was on antihypertensive (olmesartan 40 mg once daily and amlodipine 5 mg once daily) and antidiabetic (glimepiride 2 mg once daily and metformin 500 mg two times per day) medications. She has history of recurrent admissions (almost every month) at local hospital for hyponatraemia (in the range of 124–128 mEq/L) over the past 1 year. During each admission, she was given intravenous normal saline, following which she used to improve.

On presentation, she was conscious, oriented and afebrile, with body mass index 21.02 kg/m². Her pulse rate was 90/min (regular) and blood pressure 130/80 mm Hg. Her systemic examinations were normal with no signs of meningeal irritation.

Investigations

Her blood investigations showed hyponatraemia (119 mEq/L). Other investigations like complete blood count, renal and liver functions, serum potassium, calcium, magnesium, thyroid stimulating hormone and glycosylated haemoglobin were normal. Electrocardiography and chest X-ray were normal. Her urine output was normal (with regard to intake). Urine microscopy was normal and urine sodium was 50 mmol/L. Renal artery doppler was normal. Her MRI brain showed an ill-defined hypointense lesion measuring 4×4 mm in the right lateral aspect of anterior pituitary (with hypoenhancement on contrast) causing focal superior contour bulge, suggestive of pituitary microadenoma (figure 1). Ultrasound of neck and abdomen were normal. Her investigations have been displayed in table 1.

Figure 1.

MRI brain showing pituitary microadenoma.

Table 1.

Laboratory values

TSH	0.92 uIU/mL (0.4–4.0)
Free T3	2.9 pg/mL (2.3–4.2)
Free T4	1.01 ng/dL (0.6–1.24)
Sodium	119 mEq/L (135-145)
Potassium	4.0 mEq/L (3.5–5.0)
Spot urine sodium	50 mmol/L (>20)
Urine osmolality	247 mOsm/L (52–1200)
Serum osmolality	235 mOsm/L (275–295)
Serum fasting cortisol	1.18 mcg/dL (5.0–23)
Adrenocorticotropic hormone	<5 pg/mL (7.2–63.3)
Insulin like growth factor – 1	46 ng/mL (64–188)
Prolactin	26.96 ng/mL (<25)
Luteinising hormone	73 IU/L (19.3 to 100.6)
Follicle-stimulating hormone	63 mIU/mL (25.8 to 134.8)
Growth hormone	0.06 ng/mL (1–16)
Antidiuretic hormone	2 pg/mL (1–5)

TSH, thyroid stimulating hormone.

Treatment

Sodium correction was done with intravenous normal saline. She was started on oral hydrocortisone (10 mg in morning and 5 mg in evening). Her antihypertensive and antidiabetic medications were continued. As she was on hydrocortisone, she was also started on once daily dose of subcutaneous insulin degludec (10 units). Ophthalmic examination was normal.

Outcome and Follow-up

Following therapy, her sodium level started normalising; and was discharged with a value of 136 mEq/L. She was reviewed regularly and there were no further episodes of hyponatraemia over the next 6 months. Sodium levels were in the range of 136–138 mEq/L. Her antihypertensive and antidiabetic medications were continued along with oral hydrocortisone. Her repeat fasting cortisol levels, after 4 and 6 months, were normal (8 and 12 mcg/dL, respectively). Repeat MRI pituitary after 6 months did not show any increase in size of the microadenoma.

Discussion

The pituitary gland is regarded as the master gland of the body as it controls the activity of most of the other hormone secreting glands. It is a pea-sized gland situated in sella turcica, a bony hollow at the base of the skull, underneath the brain and behind the bridge of the nose. It has two parts—the anterior part producing growth hormone, luteinising hormone, follicle-stimulating hormone, prolactin, adrenocorticotropic hormone and thyroid-stimulating hormone; while the posterior part produces vasopressin or antidiuretic hormone and oxytocin. Between the anterior and posterior part lies the intermediate pituitary gland which produces melanocyte-stimulating hormone.

Pituitary adenomas are mostly sporadic. Associated germline mutations are increasingly seen with up to 43% of cases having a significant family history for pituitary adenoma. Even though, aryl hydrocarbon receptor interacting protein and other germline mutations (MEN1, CDKN1B, PRKAR1A, SDHx) may predispose to the development of pituitary adenoma, the clinical consequences of these mutations are unclear. Hence, there are no formal guidelines regarding genetic testing for patients with pituitary adenoma.^{4 5}

Usually pituitary microadenomas are non-functioning, with no pituitary dysfunction. However, about 10% of microadenomas may increase in size.⁶ The current guidelines recommend detailed endocrine evaluation in patients with pituitary macroadenomas (≥1 cm) or microadenomas (>5 mm) due to a higher prevalence of hypopituitarism.^{3 5 7} The incidence of panhypopituitarism is low among patients with pituitary microadenomas (<1 cm).² Yuen et al have reported panhypopituitarism in pituitary microadenoma with mean size of 4.2 mm.⁸ Diederich et al have observed hyponatraemia due to hypopituitarism.⁹ The probable mechanism for hypopituitarism is the adenoma compressing and damaging the pituitary tissue, and thereby interfering with hormone production.

The present case emphasises the importance of assessing the pituitary gland in case of hyponatraemia, and the hormonal levels even in the presence of microadenoma; especially in cases of recurrent hyponatraemia. Though the current guidelines exclude hormonal assessment in cases of small pituitary microadenomas, in the light of current case and a few cases reported earlier,^8–10 the tumour size may not be an appropriate exclusion criterion for assessment of hypopituitarism.

Learning points.

• Pituitary microadenoma can cause hypopituitarism and hyponatraemia.

• In contrary to current guideline, hormonal assessment should be done even in cases of small pituitary microadenoma.

• Asymptomatic pituitary microadenomas should be kept on long-term follow-up with periodic basal pituitary hormonal level estimation.

Ethics statements

Patient consent for publication

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