Diagnosis and Treatment > Signs and Symptoms > Face - change in appearance
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Search for other papers by Karen Decaestecker in
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Search for other papers by Nike Van Doninck in
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Summary
ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing’s syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing’s syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic–pituitary–axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing’s stigmata improved gradually.
Learning points:
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Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity.
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The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion.
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Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children.
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If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.
Search for other papers by Tessa Glyn in
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Search for other papers by Beverley Harris in
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Search for other papers by Kate Allen in
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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:
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Isolated central hypothyroidism is very rare, but should be considered irrespective of previous thyroid disorders.
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If clinicians have a strong suspicion that a patient may have hypothyroidism despite normal TSH, they should ensure they measure fT3 and fT4.
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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.
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Thyroid function tests should be performed routinely in patients presenting with renal impairment or a raised CK.
Search for other papers by Noor Rafhati Adyani Abdullah in
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Search for other papers by Wong Lok Chin Jason in
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Search for other papers by Azraai Bahari Nasruddin in
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Summary
Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis.
Learning points
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There is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan’s syndrome, McCune–Albright and a rare condition called pachydermoperiostosis.
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Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.
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The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.
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If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.
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Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).
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Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.
Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia
Search for other papers by Kharis Burns in
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Department of Endocrinology, Royal North Shore Hospital, St Leonards, 2065, Australia
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Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia
St Vincent's Clinical School, University of New South Wales, Sydney, 2010, Australia
Diabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, 2010, Australia
Department of Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, 2045, Australia
Search for other papers by Jenny E Gunton in
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Summary
Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its in vivo efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76 mmol/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552 nmol/l with an inappropriate ACTH of 9.3 pmol/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150 nmol/mmol with failure to suppress after 48 h of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200 nmol/day. Metyrapone was commenced at 750 mg tds. Ketoconazole was later added at 400 mg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200 mg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400 mg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged in vivo efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease.
Learning points
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Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.
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Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-β-hydroxylase and 17-α-hydroxylase, though its availability is limited in many countries.
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Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.
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Fluconazole represents a suitable alternative for the medical management of Cushing's disease and proved an effective addition to metyrapone in the management of this case.
