Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices.
Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections.
Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence.
Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol.
Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.
Although bisphosphonates (BPs) are mainly used for the treatment of osteoporosis and are generally safe, long-term use and more dosage as utilised in malignant conditions may be associated with the rare adverse event of an atypical femoral fracture (AFF). Occasionally, the risk of developing an AFF persists long after BPs are withdrawn. A 39-year-old woman who underwent chemotherapy and an autologous stem cell transplantation for multiple myeloma presented to us with history of pain in the left thigh. She had received multiple doses of oral and parenteral BPs for about 10 years in view of the underlying myeloma with osteoporosis. Her investigations showed a suppressed CTX of 192 pg/mL, and radiograph of pelvis displayed thickened cortices with beaking of the left femoral shaft, which was suggestive of an AFF. Following discontinuation of BPs, she underwent prophylactic intra-medullary nailing with which her symptoms improved. Five years later, she presented with similar complaints on the right side. Investigations showed that her bone turnover continued to be suppressed with Cross linked C- Telopeptide of type 1 collagen (CTX) of 165 pg/mL and an X-ray done showed AFF on the right side despite being off BPs. A second intra-medullary nailing was done and on follow-up, she has been symptom-free and independent in her daily activities. Discontinuation of BPs may not prevent the incident second AFF and, therefore, thus warranting long-term follow-up.
Regular screening and follow-up of patients who receive long-term bisphosphonate (BP) therapy should be done.
Discontinuation of BPs does not preclude the possibility of repeated occurrence of a second AFF.
Long-term BP therapy warrants regular monitoring and follow-up should an AFF occur
Thyroid eye disease (TED) is the most common extra-thyroidal manifestation in Graves’ disease (GD). Additional/concurrent/synchronous pathologies may be present, especially in elderly patients who present with atypical features such as non-axial (or eccentric) proptosis, absence of lid lag and restricted superior extra-ocular movements. A 70-year-old female presented with progressive proptosis of her left eye and diplopia. She was diagnosed with GD a year prior and initiated on carbimazole. On examination, she had eccentric proptosis, restricted superior extra-ocular movements and a palpable mass in the supero-temporal quadrant of the left eye. Her T3 (1.33 ng/mL) and T4 (8.85 µg/dL) were normal with carbimazole. Thyroid-stimulating hormone (TSH)-receptor antibody was positive (3.15 IU/L, reference range <1.75). MRI revealed an enhancing lesion infiltrating the left superior rectus, with concurrent characteristic muscle belly involvement bilaterally. Orbital biopsy showed atypical lymphoid cells (CD20+), suggesting marginal zone lymphoma. CT thorax and abdomen, fluorodeoxyglucose-positron emission tomography and bone marrow examination were normal. The patient was administered orbital radiotherapy for her localised lymphoma and carbimazole was continued. TED is the most common cause of orbital involvement overall and in GD. However, additional or alternative pathology may be present which requires evaluation. MRI can be a useful adjunct in these patients. Orbital lymphoma needs to be staged with workup for disseminated disease. Radiotherapy is the treatment of choice for localized disease. The index case provides evidence for synchronous presentation of dual pathology and highlights the importance of astute clinical examination as well as keeps a low threshold for MRI in selected cases.
Thyroid eye disease can co-exist with other ocular pathology, especially in elderly individuals.
Eccentric proptosis, absent lid lag and restriction of eye movements (suggesting tendon involvement) should alert towards the presence of alternative pathology.
Orbital imaging using MRI not only has greater sensitivity in diagnosing radiologically bilateral disease in patients who have unilateral involvement clinically but is also useful to identify concurrent neoplasms.
Combined pituitary hormonal deficiency (CPHD) is a rare disease that results from mutations in genes coding for transcription factors that regulate the differentiation of pituitary cells. PROP1 gene mutations are one of the etiological diagnoses of congenital panhypopituitarism, however symptoms vary depending on phenotypic expression. We present a case of psychosis in a 36-year-old female with congenital panhypopituitarism who presented with paranoia, flat affect and ideas of reference without a delirious mental state, which resolved with hormone replacement and antipsychotics. Further evaluation revealed that she had a homozygous mutation of PROP1 gene. In summary, compliance with hormonal therapy for patients with hypopituitarism appears to be effective for the prevention and treatment of acute psychosis symptoms.
Patients with PROP1 gene mutation may present with psychosis with no impairment in orientation and memory.
There is currently inadequate literature on this topic, and further study on the possible mechanisms of psychosis as a result of endocrine disturbance is required.
Compliance with hormonal therapy for patients with hypopituitarism appears to be effective for prevention and treatment of acute psychosis symptoms.
Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycaemia, which is known to occur in association with the use of sulfhydryl-containing drugs and autoimmune disorders. We describe a patient with hitherto an unreported association of IAS with ankylosing spondylitis. We have also performed and described a simplified method of polyethylene glycol (PEG) precipitation of an insulin bound antibody in the serum.
IAS should be considered in differential diagnosis of endogenous hyperinsulinemic hypoglycaemia.
Ankylosing spondylitis can be associated with IAS apart from several other autoimmune diseases.
Very high serum insulin levels (100–10 000 μU/ml) are frequently seen in IAS.
When faced with very high serum insulin before suspecting insulinoma, it is advisable that PEG precipitation of serum be done to identify antibody bound insulin.
A clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.
Spontaneous diabetic muscle infarction (DMI) is a rare and under diagnosed complication of diabetes mellitus. Clinically it presents with acute to subacute onset swelling, pain and tenderness of muscle(s) without systemic manifestations. MRI is helpful in diagnosis, exclusion of other causes and for localization of affected muscle for biopsy in atypical cases. Muscles of the thighs are commonly affected in diabetic myonecrosis (DMN). Here we present the summary of four cases seen in the last 3 years in a tertiary care centre with simultaneous or sequential involvement of multiple groups of muscles or involvement of uncommon sites. All these patients had advanced duration of diabetes with microvascular complications and poor glycemic control. Conservative management including rest and analgesics is the treatment of choice. Short-term prognosis is good but there may be recurrence.
A high index of suspicion is required for the diagnosis of DMN which can avoid inadvertent use of antibiotics.
Acute–subacute onset severe focal muscle pain in the absence of systemic symptoms in a female patient with long-standing diabetes with microvascular complications suggests DMI.
MRI is the most sensitive test for diagnosis.
Muscle biopsy should be reserved for atypical cases.
Conservative management including rest and analgesics has good outcome.
Improvement usually occurs within 6–8 weeks, but there may be recurrence.
Motor neuron disease (MND) is a progressive devastating neurodegenerative disease, which universally progresses towards death. Hence, every attempt should be made to find out if there are any treatable conditions, which can mimic MND. Herein, we describe a case of hypercalcaemia due to primary hyperparathyroidism confused as MND and subsequently cured with parathyroid surgery.
Any patient with neurological disorder should have a screening of all the common electrolytes including calcium as electrolyte imbalance can present with paralysis (e.g. hypokalaemia) to amyotrophic lateral sclerosis (e.g. hypercalcaemia).
No patient should be stamped as having MND without having a proper work-up of all its differentials as there might be a treatable condition masquerading as MND.
Carney complex (CNC) is a rare autosomal dominant syndrome characterized by pigmented lesions of the skin and mucosae along with cardiac, endocrine, cutaneous, and neural myxomatous tumors. Mutations in the PRKAR1A gene have been identified in ∼70% of the CNC cases reported worldwide. A 30-year-old male was referred to the endocrinology clinic with suspected acromegaly. He had a history of recurrent atrial myxoma for the past 8 years for which he underwent repeated surgeries. Presently, he complained of having headache, excessive snoring, sweating, and also noticed increase in his shoe size. Evaluation for acromegaly revealed elevated levels of GH in random as well as in suppressed condition. Magnetic resonance imaging scan revealed enlarged sella with microadenoma in the left anterior pituitary. Screening of PRKAR1A gene was carried out for the patient, his parents and siblings who were available and willing to undergo the test. The patient was diagnosed to have the rare CNC syndrome characterized by recurrent atrial myxoma and acromegaly due to a novel 22 bp insertion mutation in PRKAR1A which was predicted to be deleterious by in silico analysis. Screening the available family members revealed the absence of this mutation in them except the elder brother who also tested positive for this mutation. The present study reports on a novel PRKAR1A insertion mutation in a patient with acromegaly and left atrial myxoma in CNC.
Identification of a novel deleterious PRKAR1A insertion mutation causing CNC.
It is important that patients with cardiac myxoma be investigated for presence of endocrine overactivity suggestive of CNC.
PRKAR1A mutation analysis should be undertaken in such cases to confirm the diagnosis in the patients as well as first degree relatives.
This case highlights an important aspect of diagnosis, clinical course, and management of this rare condition.
We describe the clinical presentation, diagnostic and management issues in five cases of non-islet cell tumor hypoglycemia (NICTH), diagnosed at a tertiary care institute over a period of 15 years. The clinical, laboratory, and histopathological findings of these patients along with diagnostic utility of IGF2:IGF1 ratio are discussed. The mean age of presentation was 52 years, with a male predominance (3:2). Three patients presented with recurrent episodes of fasting hypoglycemia and it was detected in other two patients during hospitalization. Two patients had acromegaloid features that regressed following treatment. One patient had hypokalemia. Low levels of insulin, C-peptide, GH, and IGF1 were invariably found in all. The IGF2 level was elevated in only one patient; however, IGF2:IGF1 ratio was more than 10 in four of the five patients. The mean tumor size was 16.4 cm and mean weight was 3.6 kg. Four patients had mesenchymal tumors and one had epithelial tumor. NICTH is a rare cause of hypoglycemia. Hypoinsulinemic hypoglycemia with low IGF1 and IGF2:IGF1 ratio more than 10 is suggestive of this entity.
NICTH should be considered in patients presenting with tumor of mesenchymal origin and hypoglycemia.
Hypoinsulinemic hypoglycemia with low IGF1 is a strong biochemical evidence of NICTH.
IGF2:IGF1 ratio of more than 10 is a complementary investigation in the absence of an assay facility for IGF2.
A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery.
Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.
Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.
Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.
In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future.