Diagnosis and Treatment > Signs and Symptoms > Muscle atrophy
You are looking at 1 - 10 of 13 items
Search for other papers by Frank Gao in
Google Scholar
PubMed
Search for other papers by Stephen Hall in
Google Scholar
PubMed
Department of Medicine (Alfred), Monash University, Melbourne, Australia
Search for other papers by Leon A Bach in
Google Scholar
PubMed
Summary
Sodium/glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycaemic agents that are increasingly used in the management of type 2 diabetes mellitus (T2DM). They are now recommended as second-line pharmacotherapy (in conjunction with metformin) in patients with type 2 diabetes and established atherosclerotic heart disease, heart failure or chronic kidney disease due to their favourable effects on cardiovascular and renal outcomes. We report a case of a 69-year-old man who developed muscle pain, weakness and wasting after commencing the SGLT2 inhibitor empagliflozin. This persisted for 1 year before he underwent resistance testing, which confirmed muscle weakness. His symptoms resolved within weeks of ceasing empagliflozin, with improvement in muscle strength on clinical assessment and resistance testing and reversal of MRI changes. No other cause of myopathy was identified clinically, on biochemical assessment or imaging, suggesting that empagliflozin was the cause of his myopathy.
Learning points:
-
Empagliflozin, a commonly used SGLT2 inhibitor, was associated with myopathy.
-
A high degree of suspicion is required to diagnose drug-induced myopathy, with a temporal relationship between starting the medication and symptom onset being the main indicator.
-
Recognition of drug-induced myopathy is essential, as discontinuation of the offending drug typically improves symptoms.
Search for other papers by N Siddique in
Google Scholar
PubMed
Search for other papers by R Durcan in
Google Scholar
PubMed
Search for other papers by S Smyth in
Google Scholar
PubMed
Search for other papers by T Kyaw Tun in
Google Scholar
PubMed
Search for other papers by S Sreenan in
Google Scholar
PubMed
Search for other papers by J H McDermott in
Google Scholar
PubMed
Summary
We present three cases of acute diabetic neuropathy and highlight a potentially underappreciated link between tightening of glycaemic control and acute neuropathies in patients with diabetes. Case 1: A 56-year-old male with poorly controlled type 2 diabetes (T2DM) was commenced on basal-bolus insulin. He presented 6 weeks later with a diffuse painful sensory neuropathy and postural hypotension. He was diagnosed with treatment-induced neuropathy (TIN, insulin neuritis) and obtained symptomatic relief from pregabalin. Case 2: A 67-year-old male with T2DM and chronic hyperglycaemia presented with left lower limb pain, weakness and weight loss shortly after achieving target glycaemia with oral anti-hyperglycaemics. Neurological examination and neuro-electrophysiological studies suggested diabetic lumbosacral radiculo-plexus neuropathy (DLPRN, diabetic amyotrophy). Pain and weakness resolved over time. Case 3: A 58-year-old male was admitted with blurred vision diplopia and complete ptosis of the right eye, with intact pupillary reflexes, shortly after intensification of glucose-lowering treatment with an SGLT2 inhibitor as adjunct to metformin. He was diagnosed with a pupil-sparing third nerve palsy secondary to diabetic mononeuritis which improved over time. While all three acute neuropathies have been previously well described, all are rare and require a high index of clinical suspicion as they are essentially a diagnosis of exclusion. Interestingly, all three of our cases are linked by the development of acute neuropathy following a significant improvement in glycaemic control. This phenomenon is well described in TIN, but not previously highlighted in other acute neuropathies.
Learning points:
-
A link between acute tightening of glycaemic control and acute neuropathies has not been well described in literature.
-
Clinicians caring for patients with diabetes who develop otherwise unexplained neurologic symptoms following a tightening of glycaemic control should consider the possibility of an acute diabetic neuropathy.
-
Early recognition of these neuropathies can obviate the need for detailed and expensive investigations and allow for early institution of appropriate pain-relieving medications.
Search for other papers by Alessandro Rossini in
Google Scholar
PubMed
Search for other papers by Francesca Perticone in
Google Scholar
PubMed
Search for other papers by Laura Frosio in
Google Scholar
PubMed
Search for other papers by Marco Schiavo Lena in
Google Scholar
PubMed
Search for other papers by Roberto Lanzi in
Google Scholar
PubMed
Summary
ACTH-secreting pheochromocytoma is a very rare cause of Cushing’s syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We report the case of a 45-year-old female patient with a 3 cm, high-density, left adrenal mass, diagnosed as an ACTH-secreting pheochromocytoma. The biochemical sensitivity of the tumor to somatostatin analogues was tested by a 100 μg s.c. octreotide administration, which led to an ACTH and cortisol reduction of 50 and 25% respectively. In addition to alpha and beta blockers, preoperative approach to laparoscopic adrenalectomy included octreotide, a somatostatin analogue, together with ketoconazole, in order to achieve an adequate pre-surgical control of cortisol release. Histopathological assessment confirmed an ACTH-secreting pheochromocytoma expressing type 2 and 5 somatostatin receptors (SSTR-2 and -5).
Learning points:
-
ACTH-secreting pheochromocytomas represent a rare and severe condition, characterized by high morbidity and mortality risk.
-
Surgical removal of the adrenal mass is the gold standard treatment, but adequate medical therapy is required preoperatively to improve the surgical outcome and to avoid major complications.
-
Somatostatin analogs, in addition to other medications, may represent a useful therapeutic option for the presurgical management of selected patients.
-
In this sense, the octreotide challenge test is a useful tool to predict favorable therapeutic response to the treatment.
Search for other papers by Karen Decaestecker in
Google Scholar
PubMed
Search for other papers by Veerle Wijtvliet in
Google Scholar
PubMed
Search for other papers by Peter Coremans in
Google Scholar
PubMed
Search for other papers by Nike Van Doninck in
Google Scholar
PubMed
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:
-
Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity.
-
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.
-
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.
-
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.
Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia
Search for other papers by S F Wan Muhammad Hatta in
Google Scholar
PubMed
Search for other papers by L Kandaswamy in
Google Scholar
PubMed
Search for other papers by C Gherman-Ciolac in
Google Scholar
PubMed
Search for other papers by J Mann in
Google Scholar
PubMed
Search for other papers by H N Buch in
Google Scholar
PubMed
Summary
Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing’s syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test.
Learning points:
-
Cushing’s syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.
-
Proximal lower-limb girdle myopathy is common in Cushing’s syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.
-
Treatment of Cushing’s myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.
Search for other papers by Carlos Tavares Bello in
Google Scholar
PubMed
Search for other papers by Patricia Cipriano in
Google Scholar
PubMed
Search for other papers by Vanessa Henriques in
Google Scholar
PubMed
Search for other papers by João Sequeira Duarte in
Google Scholar
PubMed
Search for other papers by Conceição Canas Marques in
Google Scholar
PubMed
Summary
Granular cell tumours (GCT) are rare, slow-growing, benign neoplasms that are usually located in the head and neck. They are more frequent in the female gender and typically have an asymptomatic clinical course, being diagnosed only at autopsy. Symptomatic GCT of the neurohypophysis are exceedingly rare, being less than 70 cases described so far. The authors report on a case of a 28-year-old male that presented to the Endocrinology clinic with clinical and biochemical evidence of hypogonadism. He also reported minor headaches without any major visual symptoms. Further laboratory tests confirmed hypopituitarism (hypogonadotrophic hypogonadism, central hypothyroidism and hypocortisolism) and central nervous system imaging revealed a pituitary macroadenoma. The patient underwent transcranial pituitary adenoma resection and the pathology report described a GCT of the neurohypophysis with low mitotic index. The reported case is noteworthy for the rarity of the clinicopathological entity.
Learning points:
-
Symptomatic GCTs are rare CNS tumours whose cell of origin is not well defined that usually give rise to visual symptoms, headache and endocrine dysfunction.
-
Imaging is quite unspecific and diagnosis is difficult to establish preoperatively.
-
Surgical excision is challenging due to lesion’s high vascularity and propensity to adhere to adjacent structures.
-
The reported case is noteworthy for the rarity of the clinicopathological entity.
Search for other papers by Ken Takeshima in
Google Scholar
PubMed
Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Search for other papers by Tatsuya Ishibashi in
Google Scholar
PubMed
Search for other papers by Shintaro Kawai in
Google Scholar
PubMed
Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Search for other papers by Jinsoo Koh in
Google Scholar
PubMed
Search for other papers by Hidefumi Ito in
Google Scholar
PubMed
Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Summary
Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA) axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.
Learning points:
-
DM1 patients could be affected by a variety of multiple endocrinopathies.
-
Our patients with DM1 presented rare combinations of multiple endocrinopathies; diabetes mellitus, combined form of primary and secondary hypogonadism and dysfunction of HPA axis.
-
Testosterone treatment of hypogonadism in patients with DM1 could improve body composition.
-
The patients with DM1 should be assessed endocrine functions and treated depending on the degree of each endocrine dysfunction.
Search for other papers by Lourdes Balcázar-Hernández in
Google Scholar
PubMed
Search for other papers by Guadalupe Vargas-Ortega in
Google Scholar
PubMed
Search for other papers by Yelitza Valverde-García in
Google Scholar
PubMed
Search for other papers by Victoria Mendoza-Zubieta in
Google Scholar
PubMed
Search for other papers by Baldomero González-Virla in
Google Scholar
PubMed
Summary
The craniopharyngiomas are solid cystic suprasellar tumors that can present extension to adjacent structures, conditioning pituitary and hypothalamic dysfunction. Within hypothalamic neuroendocrine dysfunction, we can find obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, imbalances in the regulation of body temperature, thirst, heart rate and/or blood pressure and alterations in dietary intake (like anorexia). We present a rare case of anorexia–cachexia syndrome like a manifestation of neuroendocrine dysfunction in a patient with a papillary craniopharyngioma. Anorexia–cachexia syndrome is a complex metabolic process associated with underlying illness and characterized by loss of muscle with or without loss of fat mass and can occur in a number of diseases like cancer neoplasm, non-cancer neoplasm, chronic disease or immunodeficiency states like HIV/AIDS. The role of cytokines and anorexigenic and orexigenic peptides are important in the etiology. The anorexia–cachexia syndrome is a clinical entity rarely described in the literature and it leads to important function limitation, comorbidities and worsening prognosis.
Learning points:
-
Suprasellar lesions can result in pituitary and hypothalamic dysfunction.
-
The hypothalamic neuroendocrine dysfunction is commonly related with obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, but rarely with anorexia–cachexia.
-
Anorexia–cachexia syndrome is a metabolic process associated with loss of muscle, with or without loss of fat mass, in a patient with neoplasm, chronic disease or immunodeficiency states.
-
Anorexia–cachexia syndrome results in important function limitation, comorbidities that influence negatively on treatment, progressive clinical deterioration and bad prognosis that can lead the patient to death.
-
Anorexia–cachexia syndrome should be suspected in patients with emaciation and hypothalamic lesions.
Search for other papers by Teresa Rego in
Google Scholar
PubMed
Search for other papers by Fernando Fonseca in
Google Scholar
PubMed
Search for other papers by Stéphanie Espiard in
Google Scholar
PubMed
Search for other papers by Karine Perlemoine in
Google Scholar
PubMed
Search for other papers by Jérôme Bertherat in
Google Scholar
PubMed
Search for other papers by Ana Agapito in
Google Scholar
PubMed
Summary
PBMAH is a rare etiology of Cushing syndrome (CS). Familial clustering suggested a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat-containing 5 (ARMC5) gene. A 70-year-old female patient was admitted due to left femoral neck fracture in May 2014, in Orthopedics Department. During hospitalization, hypertension (HTA) and hypokalemia were diagnosed. She presented with clinical signs of hypercortisolism and was transferred to the Endocrinology ward for suspected CS. Laboratory workup revealed: ACTH <5 pg/mL; urinary free cortisol (UFC), 532 µg/24 h (normal range: 20–90); failure to suppress the low-dose dexamethasone test (0.5 mg every 6 h for 48 h): cortisol 21 µg/dL. Abdominal magnetic resonance imaging (MRI) showed enlarged nodular adrenals (right, 55 × 54 × 30 mm; left, 85 × 53 × 35 mm), and she was submitted to bilateral adrenalectomy. In 2006, this patient’s 39-year-old daughter had been treated by one of the authors. She presented with severe clinical and biological hypercortisolism. Computed tomography (CT) scan showed massively enlarged nodular adrenals with maximal axis of 15 cm for both. Bilateral adrenalectomy was performed. In this familial context of PBMAH, genetic study was performed. Leucocyte DNA genotyping identified in both patients the same germline heterozygous ARMC5 mutation in exon 1 c.172_173insA p.I58Nfs*45. The clinical cases herein described have an identical phenotype with severe hypercortisolism and huge adrenal glands, but different ages at the time of diagnosis. Current knowledge of inheritance of this disease, its insidious nature and the well-known deleterious effect of hypercortisolism favor genetic study to timely identify and treat these patients.
Learning points:
-
PBMAH is a rare etiology of CS, characterized by functioning adrenal macronodules and variable cortisol secretion.
-
The asymmetric/asynchronous involvement of only one adrenal gland can also occur, making disease diagnosis a challenge.
-
Familial clustering suggests a genetic cause that was recently confirmed, after identification of inactivating germline mutations in armadillo repeat-containing 5 (ARMC5) gene.
-
The insidious nature of this disease and the well-known deleterious effect of hypercortisolism favor genetic study of other family members, to diagnose and treat these patients timely.
-
As ARMC5 is expressed in many organs and recent findings suggest an association of PBMAH and meningioma, a watchful follow-up is required.
Search for other papers by A Pazderska in
Google Scholar
PubMed
Search for other papers by S Crowther in
Google Scholar
PubMed
Search for other papers by P Govender in
Google Scholar
PubMed
Departments of Surgery, Trinity College, Dublin, Ireland
Search for other papers by K C Conlon in
Google Scholar
PubMed
Departments of Endocrinology, Trinity College, Dublin, Ireland
Search for other papers by M Sherlock in
Google Scholar
PubMed
Departments of Endocrinology, Trinity College, Dublin, Ireland
Search for other papers by J Gibney in
Google Scholar
PubMed
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.
