Clinical Overview > Hormone > ACTH

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M J Trott Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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G Farah Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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V J Stokes Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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L M Wang Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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A B Grossman Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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Summary

We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.

Learning points

  • Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndrome

  • There is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)

  • The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohort

  • An exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populations

  • The relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases

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Ya-Wun Guo Department of Medicine, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan
Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan

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Chii-Min Hwu Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

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Justin Ging-Shing Won Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

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Chia-Huei Chu Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
Department of Otorhinolaryngology-Head and Neck Surgery, Division of Otology, Taipei Veterans General Hospital, Taipei, Taiwan

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Liang-Yu Lin Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

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Summary

A functional lesion in corticotrophin (ACTH)-independent Cushing’s syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and 131I-6β-iodomethyl-19-norcholesterol (131I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and 131I-NP-59 scintigraphy are good diagnostic methods for Cushing’s syndrome presenting with bilateral adrenal masses.

Learning points

  • The clinical presentation of Cushing’ syndrome includes symptoms and signs of fat redistribution and protein-wasting features.

  • The diagnosis of patients with ACTH-independent Cushing’s syndrome with bilateral adrenal masses is challenging for localisation of the lesion.

  • Both adrenal venous sampling and 131I-NP-59 scintigraphy are good methods to use in these patients with Cushing’s syndrome presenting with bilateral adrenal masses.

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A Pazderska Departments of Endocrinology, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland

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S Crowther Departments of Cellular Pathology, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland

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P Govender Departments of Radiology, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland

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K C Conlon Departments of Professional Surgical Unit, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland
Departments of Surgery, Trinity College, Dublin, Ireland

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M Sherlock Departments of Endocrinology, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland
Departments of Endocrinology, Trinity College, Dublin, Ireland

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J Gibney Departments of Endocrinology, Adelaide and Meath Hospitals, incorporating the National Children’s Hospital, Tallaght, Dublin 24, Ireland
Departments of Endocrinology, Trinity College, Dublin, Ireland

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Summary

Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia.

Learning points

  • AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.

  • Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.

  • Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing’s syndrome.

Open access
Jasmeet Kaur Division of Biomedical Science, Department of Biochemistry, Mercer University School of Medicine and Memorial University Medical Center, Hoskins Research Building, 4700 Waters Avenue, Savannah, Georgia, 31404, USA

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Luis Casas Division of Endocrinology, Department of Pediatrics, University of North Dakota, Fargo, North Dakota, USA

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Himangshu S Bose Division of Biomedical Science, Department of Biochemistry, Mercer University School of Medicine and Memorial University Medical Center, Hoskins Research Building, 4700 Waters Avenue, Savannah, Georgia, 31404, USA
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, 31404, USA

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Summary

Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions.

Learning points

  • STAR mutations cause lipoid CAH.

  • This is a pure population from a caucasian family.

  • Mutation ablated STAR activity.

  • The mutation resulted in loosely folded conformation of STAR.

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Jeremy M W Kirk Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nalin Wickramasuriya Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Nicholas J Shaw Department of Endocrinology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

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Summary

Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.

Learning points

  • Girls with primary and secondary gonadal failure require assistance with pubertal induction.

  • Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.

  • Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.

  • Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.

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Kharis Burns Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, 2145, Australia
Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia

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Darshika Christie-David Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, 2145, Australia
Department of Endocrinology, Royal North Shore Hospital, St Leonards, 2065, Australia

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Jenny E Gunton Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, 2145, Australia
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

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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

  • 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.

  • 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.

  • Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.

  • 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.

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Harish Venugopal Department of Diabetes and Endocrinology, Gold Coast, University Hospital, School of Medicine, Griffith University, 1 Hospital Boulevard, Southport, QLD 4215QLD 4215, Queensland, Australia

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Katherine Griffin Department of Diabetes and Endocrinology, Gold Coast, University Hospital, School of Medicine, Griffith University, 1 Hospital Boulevard, Southport, QLD 4215QLD 4215, Queensland, Australia

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Saima Amer Department of Diabetes and Endocrinology, Gold Coast, University Hospital, School of Medicine, Griffith University, 1 Hospital Boulevard, Southport, QLD 4215QLD 4215, Queensland, Australia

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Summary

Resection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy.

Learning points

  • Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging.

  • Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence needs to be managed aggressively.

  • Bilateral adrenalectomy should be considered when medical treatment is ineffective or poorly tolerated.

  • Percutaneous adrenal ablation may be considered in patients who are otherwise unable to undergo bilateral adrenalectomy.

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Asma Deeb Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, UAE

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Hana Al Suwaidi Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, UAE

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Salima Attia Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, UAE

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Ahlam Al Ameri Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, UAE

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Summary

Combined17α-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Hypertension and hypokalemia are essential presenting features. We report an Arab family with four affected XX siblings. The eldest presented with abdominal pain and was diagnosed with a retroperitoneal malignant mixed germ cell tumour. She was hypertensive and hypogonadal. One sibling presented with headache due to hypertension while the other two siblings were diagnosed with hypertension on a routine school check. A homozygous R96Q missense mutation in P450c17 was detected in the index case who had primary amenorrhea and lack of secondary sexual characters at 17 years. The middle two siblings were identical twins and had no secondary sexual characters at the age of 14. All siblings had hypokalemia, very low level of adrenal androgens, high ACTH and high levels of aldosterone substrates. Treatment was commenced with steroid replacement and puberty induction with estradiol. The index case had surgical tumor resection and chemotherapy. All siblings required antihypertensive treatment and the oldest remained on two antihypertensive medications 12 years after diagnosis. Her breast development remained poor despite adequate hormonal replacement. Combined 17α-hydroxylase/17,20-lyase deficiency is a rare condition but might be underdiagnosed. It should be considered in young patients presenting with hypertension, particularly if there is a family history of consanguinity and with more than one affected sibling. Antihypertensive medication might continue to be required despite adequate steroid replacement. Breast development may remain poor in mutations causing complete form of the disease.

Learning points

  • Endocrine hypertension due to rarer forms of CAH should be considered in children and adolescents, particularly if more than one sibling is affected and in the presence of consanguinity.

  • 17α-hydroxylase/17,20-lyase deficiency is a rare form of CAH but might be underdiagnosed.

  • Blood pressure measurement should be carried out in all females presenting with hypogonadism.

  • Anti-hypertensive medications might be required despite adequate steroid replacement.

  • Initial presenting features might vary within affected members of the same family.

  • Adverse breast development might be seen in the complete enzyme deficiency forms of the disease.

Open access
Avinash Suryawanshi Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia
Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia

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Timothy Middleton Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia
Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia

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Kirtan Ganda Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia
Concord Clinical School, The University of Sydney, Sydney, New South Wales, 2139, Australia

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Summary

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition caused by mutations in the ABCD1 gene that result in accumulation of very long chain fatty acids (VLCFAs) in various tissues. This leads to demyelination in the CNS and impaired steroidogenesis in the adrenal cortex and testes. A 57-year-old gentleman was referred for the assessment of bilateral gynaecomastia of 6 months duration. He had skin hyperpigmentation since 4 years of age and spastic paraparesis for the past 15 years. Physical examination findings included generalised hyperpigmentation (including skin, buccal mucosa and palmar creases), blood pressure of 90/60 mmHg, non-tender gynaecomastia and bilateral hypoplastic testes. Lower limb findings were those of a profoundly ataxic gait associated with significant paraparesis and sensory loss. Primary adrenal insufficiency was confirmed and investigations for gynaecomastia revealed normal testosterone with mildly elevated luteinising hormone level and normal prolactin. The combination of primary adrenal insufficiency (likely childhood onset), partial testicular failure (leading to gynaecomastia) and spastic paraparesis suggested X-ALD as a unifying diagnosis. A serum VLCFA panel was consistent with X-ALD. Subsequent genetic testing confirmed the diagnosis. Treatment with replacement doses of corticosteroid resulted in improvement in blood pressure and increased energy levels. We have reported the case of a 57-year-old man with a very late diagnosis of X-ALD manifested by childhood onset of primary adrenal insufficiency followed by paraparesis and primary hypogonadism in adulthood. Thus, X-ALD should be considered as a possibility in a patient with non-autoimmune primary adrenal insufficiency and neurological abnormalities.

Learning points

  • Adult patients with X-ALD may be misdiagnosed as having multiple sclerosis or idiopathic spastic paraparesis for many years before the correct diagnosis is identified.

  • Screening for X-ALD with a VLCFA panel should be strongly considered in male children with primary adrenal insufficiency and in male adults presenting with non-autoimmune primary adrenal insufficiency.

  • Confirmation of a genetic diagnosis of X-ALD can be very useful for a patient's family as genetic testing enables detection of pre-symptomatic female heterozygotes who can then be offered pre-natal testing to avoid transmission of the disease to male offsprings.

Open access
Rémi Goupil Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia
Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, H4J 1C5, Canada

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Martin Wolley Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia

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Jacobus Ungerer Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland, 4001, Australia

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Brett McWhinney Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland, 4001, Australia

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Kuniaki Mukai Department of Biochemistry, Medical Education Center, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan

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Mitsuhide Naruse Department of Endocrinology, Metabolism and Hypertension, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

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Richard D Gordon Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia

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Michael Stowasser Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia

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Summary

In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was measured during AVS to successfully circumvent this problem. A 55-year-old hypertensive male had raised plasma aldosterone/renin ratios and PA confirmed by fludrocortisone suppression testing. Failure of plasma cortisol to suppress overnight following dexamethasone and persistently suppressed corticotrophin were consistent with adrenal hypercortisolism. On AVS, comparison of adrenal and peripheral A/F ratios (left 5.7 vs peripheral 1.0; right 1.7 vs peripheral 1.1) suggested bilateral aldosterone production, with the left gland dominant but without contralateral suppression. However, using aldosterone/metanephrine ratios (left 9.7 vs peripheral 2.4; right 1.3 vs peripheral 2.5), aldosterone production lateralized to the left with good contralateral suppression. The patient underwent left laparoscopic adrenalectomy with peri-operative glucocorticoid supplementation to prevent adrenal insufficiency. Pathological examination revealed adrenal cortical adenomas producing both cortisol and aldosterone within a background of aldosterone-producing cell clusters. Hypertension improved and cured of PA and hypercortisolism were confirmed by negative post-operative fludrocortisone suppression and overnight 1 mg dexamethasone suppression testing. Routine dexamethasone suppression testing in patients with PA permits detection of concurrent hypercortisolism which can confound AVS results and cause unilateral PA to be misdiagnosed as bilateral with patients thereby denied potentially curative surgical treatment. In such patients, measurement of plasma metanephrine during AVS may overcome this issue.

Learning points

  • Simultaneous autonomous overproduction of cortisol and aldosterone is increasingly recognised although still apparently uncommon.

  • Because cortisol levels are used during AVS to correct for differences in dilution of adrenal with non-adrenal venous blood when assessing for lateralisation, unilateral cortisol overproduction with contralateral suppression could confound the interpretation of AVS results

  • Measuring plasma metanephrine during AVS to calculate lateralisation ratios may circumvent this problem.

Open access