An Endocrine Pitfall: A Case of Secondary Hypothyroidism Unmasked by a Pituitary Macroadenoma in a Patient with Previous Primary Hypothyroidism

Case History

A 51-year-old woman was admitted to the acute medical unit with a three-month history of fatigue, nausea, abdominal pain, postural symptoms, dizziness, and unintended weight loss of 20kg. Six weeks prior, she attended the emergency department (ED) with viral symptoms, generalised aches and pain, and tenderness in the joints. She was influenza A positive and was subsequently treated with oseltamivir and prednisolone 15 mg daily for a week. Prednisolone dose was reduced by 5 mg every week in the next 2 weeks. However, she did not recover completely from her presenting symptoms. She continued to feel tired and lethargic since discharge from ED. Hence, she had been off work, which resulted in the current admission.

The past medical history includes rheumatoid arthritis, primary hypothyroidism, premature ovarian failure (POF), hypertension, lichen planus, and lichen sclerosis. She has two children, 27 and 15 years of age.

When rheumatoid arthritis was first diagnosed 35 years ago, she was treated with high dose steroids for 20 years until she went on to immunotherapy, Rituximab. She managed to stop high dose steroid therapy completely. At the same time, she was diagnosed with POF and HRT was initiated. However, in the last 5 years, she needed steroid mouth wash for lichen planus and topical steroid for lichen sclerosis intermittently. Thyroid function has been stable on levothyroxine 50mcg daily for the last 12 years.

On examination, she was afebrile, pale and hypotensive (BP 85/55 mmHg) with a significant postural drop. Cardiovascular, abdominal, and neurological assessments were unremarkable.

Full blood count, liver function, renal function and electrolytes were all within normal limits. Infection screen was negative. Inflammatory markers were normal. Recent upper GI endoscopy carried out, due to nausea and weight loss, did not reveal any significant findings accounting for her symptoms. Thyroid function (TFT) on this admission revealed completely suppressed TSH(<0.05mU/l), with low T4(8.5 pmol/l) and lowT3(<2pmol/l). Previously, TSH was in the normal range (1.5-2.2 mU/l) while taking levothyroxine 50mcg daily.

Table 1. Results of thyroid function

Thyroid function tests may be interpreted as

a. Inadequate dose of levothyroxine 50 mcg.
b. Poor compliance with levothyroxine 50 mcg.
c. Patient was taking higher dose of levothyroxine than the prescribed dose of 50 mcg daily, but blood sample was taken before medication was administered on the day of the blood test on current admission.
d. Primary hypothyroidism transformed into secondary hypothyroidism (central or pituitary cause).

The most likely cause is (d).

Although TFTs were completely stable on 50 mcg of levothyroxine for the past 12 years, the suggestive of current admission is secondary hypothyroidism. This prompted further investigations. Both 9am cortisol (<28 nmol/L) and ACTH (3.5 ng/L) were completely suppressed. Short synacthen test showed inadequate response. Other pituitary profile revealed low prolactin (34 mU/L), low oestradiol (<88 pmol/l) and low gonadotrophins (LH 0.4 U/l and FSH 3.3 U/l), normal IGF-1 and growth hormone. Biochemical picture of hypopituitarism fits in with her presenting clinical symptoms. This further prompted urgent MRI scan of the pituitary gland, which demonstrated a 1.6x 1.3x 1.3cm pituitary macroadenoma with no compression of nearby structures.

She was immediately treated with intravenous (IV) hydrocortisone followed by oral hydrocortisone replacement. Levothyroxine dose was also increased from 50 mcg to 75 mcg, 24 hrs after IV hydrocortisone administration. Patient was referred to endocrinology and pituitary multidisciplinary team urgently.

On further probing, the patient recalled having severe headache of a week duration, 3 months prior to her presentation to ED with viral symptoms. Since having the headache, patient noticed extreme fatigue, nausea, loss of appetite, unintentional loss of weight without any other upper gastrointestinal symptoms and light headedness. There were no visual symptoms or visual field defect.

It is likely that she may have had severe headache from silent pituitary apoplexy resulting in hypopituitarism. However, patient felt that the headache and other symptoms she experienced 3 months prior to her current admission, were not relevant and hence did not mention at all until specifically questioned.

A 3-week course of steroid treatment was given for flare up of rheumatoid arthritis in ED without realising that the patient was gradually exhibiting signs and symptoms of hypopituitarism, saved her from severe adrenal crisis, which can potentially be fatal. On the other hand, this interval replacement masked symptoms of hypoadrenalism and subsequently early recognition of hypopituitarism, delaying the diagnosis of pituitary apoplexy of macroadenoma.

Fig 1. MRI scan of the pituitary

Table 2. Results of other investigations during acute admission

Discussion

Secondary hypothyroidism is a rare and often overlooked diagnosis, particularly in patients with a known history of primary hypothyroidism. In the acute medical setting, subtle biochemical changes can easily be missed or misattributed to non-thyroidal illness. However, timely recognition is essential to establish the underlying diagnosis and prevent significant morbidity from evolving hypopituitarism¹,².

Pituitary macroadenomas (>10 mm) can lead to gradual hypopituitarism. Apoplexy, a haemorrhagic or ischaemic event within a pituitary tumour, may be clinically silent or mimic common conditions such as viral illness³. In this case, recognition of secondary hypothyroidism led to further investigations and diagnosis of hypopituitarism. Steroid exposure for a totally unrelated condition, i.e flare up of rheumatoid arthritis, masked symptoms of adrenal insufficiency and contributed to delayed recognition⁴.

The suppressed TSH in the presence of low T3 and T4 suggest secondary hypothyroidism⁵. Increasing levothyroxine dose without cortisol replacement can precipitate adrenal crisis due to accelerated cortisol metabolism⁶. Hence, corticosteroid replacement must precede thyroid hormone adjustment⁷.

This case highlights the importance of reassessing a “stable” endocrine diagnosis when clinical and biochemical patterns diverge. A detailed history and pattern recognition can uncover a hidden pathology and prevent serious complications.

Conclusion

This case highlights the diagnostic challenge of hypopituitarism unmasked by secondary hypothyroidism, particularly when it evolves silently in a patient with primary thyroid disease. Revisiting the history, asking relevant questions, early imaging, hormone profiling and multidisciplinary coordination are essential for safe and effective management.

Learning points

1. Reassess the diagnosis: New symptoms in patients with stable hypothyroidism warrant re-evaluation.
2. Think central casue: Suppressed TSH with low T4 and T3 should prompt further investigations to identify the aetiology of secondary hypothyroidism.
3. Check cortisol first: Always exclude adrenal insufficiency before initiating or increasing thyroid hormone therapy.
4. Ask again: Retrospective history-taking often uncovers key diagnostic clues, such as headache suggestive of apoplexy.

References

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2. Melmed S. (2020) Pituitary tumors. In: Williams Textbook of Endocrinology. 14th ed. Elsevier;. p. 251–83.
3. Karavitaki N, Wass JA. (2006) Epidemiology, diagnosis and management of non-functioning pituitary adenomas. Endocrinol Metab Clin North Am. 35(1):151–67.
4. Rajasekaran S, Vanderpump M, Baldeweg SE. (2011) UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf) ;74(1):9–20.
5. Briet C, Salenave S, Chanson P. (2015) Pituitary apoplexy. Endocrinol Metab Clin North Am.;44(1):199–209.
6. Molitch ME. (2017) Diagnosis and treatment of pituitary adenomas: a review. JAMA;317(5):516–24.
7. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al.(2016) Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab;101(2):364–89.
8. Fleseriu M, Hashim IA, Karavitaki N, Melmed S. (2011) Pituitary incidentalomas: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab;96(4):894–904.

Author information

Zin Zin Htike ¹, Banya Thet Paing ², Hnin Thandar Aung ³

1. MMBS, FRCP, PhD, Consultant Physician (Diabetes & Endocrinology) Nottingham University Hospitals NHS Trust, Nottingham, UK, Training Program Director of East Midlands Deanery.
2. MBBS, Trust Grade SHO, Nottingham University Hospitals NHS Trust, Nottingham, UK.
3. MBBS, Trust Grade SHO, Nottingham University Hospitals NHS Trust, Nottingham, UK.