Diagnosis and Treatment > Signs and Symptoms
Search for other papers by Tessa Glyn in
Google Scholar
PubMed
Search for other papers by Beverley Harris in
Google Scholar
PubMed
Search for other papers by Kate Allen in
Google Scholar
PubMed
Summary
We present the case of a 57-year-old lady who had a delayed diagnosis of central hypothyroidism on a background of Grave’s thyrotoxicosis and a partial thyroidectomy. During the twenty years following her partial thyroidectomy, the patient developed a constellation of symptoms and new diagnoses, which were investigated by numerous specialists from various fields, namely rheumatology, renal and respiratory. She developed significantly impaired renal function and raised creatine kinase (CK). She was also referred to a tertiary neurology service for investigation of myositis, which resulted in inconclusive muscle biopsies. Recurrently normal TSH results reassured clinicians that this did not relate to previous thyroid dysfunction. In 2015, she developed increased shortness of breath and was found to have a significant pericardial effusion. The clinical biochemist reviewed this lady’s blood results and elected to add on a free T4 (fT4) and free T3 (fT3), which were found to be <0.4 pmol/L (normal range (NR): 12–22 pmol/L) and 0.3 pmol/L (NR: 3.1–6.8 pmol/L), respectively. She was referred urgently to the endocrine services and commenced on Levothyroxine replacement for profound central hypothyroidism. Her other pituitary hormones and MRI were normal. In the following year, her eGFR and CK normalised, and her myositis symptoms, breathlessness and pericardial effusion resolved. One year following initiation of Levothyroxine, her fT4 and fT3 were in the normal range for the first time. This case highlights the pitfalls of relying purely on TSH for excluding hypothyroidism and the devastating effect the delay in diagnosis had upon this patient.
Learning points:
-
Isolated central hypothyroidism is very rare, but should be considered irrespective of previous thyroid disorders.
-
If clinicians have a strong suspicion that a patient may have hypothyroidism despite normal TSH, they should ensure they measure fT3 and fT4.
-
Laboratories that do not perform fT3 and fT4 routinely should review advice sent to requesting clinicians to include a statement explaining that a normal TSH excludes primary but not secondary hypothyroidism.
-
Thyroid function tests should be performed routinely in patients presenting with renal impairment or a raised CK.
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by W K M G Amarawardena in
Google Scholar
PubMed
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by K D Liyanarachchi in
Google Scholar
PubMed
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by J D C Newell-Price in
Google Scholar
PubMed
Search for other papers by R J M Ross in
Google Scholar
PubMed
Search for other papers by D Iacovazzo in
Google Scholar
PubMed
Search for other papers by M Debono in
Google Scholar
PubMed
Summary
The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test. Insulin-like growth factor 1 (IGF1) was 1710 µg/L (103–310 µg/L) and mean growth hormone (GH) was >600 U/L. MRI scan showed a 4 cm pituitary macroadenoma with suprasellar extension and right-sided cavernous sinus invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for GH. Postoperative investigations showed uncontrolled disease (IGF1:1474 µg/L, mean GH:228 U/L) and residual tumour in the cavernous sinus. She received external beam fractionated radiation. Over the years, she received octreotide LAR (up to 30 mg), lanreotide (up to 120 mg) two weekly, cabergoline, pegvisomant and stereotactic radiosurgery to no avail. Only pegvisomant resulted in an element of disease control; however, this had to be stopped due to abnormal liver function tests. Fifteen years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a month, her IGF1 dropped and has remained within the normal range (103–310 µg/L). Pasireotide has been well tolerated, and there has been significant clinical improvement. Somatostatin receptor subtyping revealed a positivity score of two for both sst5 and sst2a subtypes.
Learning points:
-
Age, size of the tumour, GH levels on presentation, histopathological type and the somatostatin receptor status of the tumour in acromegaly should be reviewed in patients who poorly respond to first-generation somatostatin receptor ligands.
-
Tumours that respond poorly to first-generation somatostatin receptor ligands, especially sparsely granulated somatotroph adenomas, can respond to pasireotide and treatment should be considered early in the management of resistant tumours.
-
Patients with membranous expression of sst5 are likely to be more responsive to pasireotide.
