Diagnosis and Treatment > Signs and Symptoms

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Eleanor P Thong Department of Endocrinology, Monash Health, Clayton, Australia
Monash Centre for Health Research and Implementation, Clayton, Australia

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Sarah Catford Department of Endocrinology, Monash Health, Clayton, Australia
Hudson Institute of Medical Research, Clayton, Australia

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Julie Fletcher Department of Anatomical Pathology, Concord Repatriation General Hospital, Concord, Australia

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Phillip Wong Department of Endocrinology, Monash Health, Clayton, Australia
Hudson Institute of Medical Research, Clayton, Australia

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Peter J Fuller Department of Endocrinology, Monash Health, Clayton, Australia
Hudson Institute of Medical Research, Clayton, Australia

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Helena Teede Department of Endocrinology, Monash Health, Clayton, Australia
Monash Centre for Health Research and Implementation, Clayton, Australia

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Frances Milat Department of Endocrinology, Monash Health, Clayton, Australia
Hudson Institute of Medical Research, Clayton, Australia

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Summary

The association between type 1 diabetes mellitus (T1DM) and bone health has garnered interest over the years. Fracture risk is known to be increased in individuals with T1DM, although bone health assessment is not often performed in the clinical setting. We describe the case of a 21-year-old male with longstanding T1DM with multilevel vertebral fractures on imaging, after presenting with acute back pain without apparent trauma. Dual-energy X-ray absorptiometry (DXA) revealed significantly reduced bone mineral density at the lumbar spine and femoral neck. Extensive investigations for other secondary or genetic causes of osteoporosis were unremarkable, apart from moderate vitamin D deficiency. High-resolution peripheral quantitative computed tomography and bone biospy revealed significant alterations of trabecular bone microarchitecture. It later transpired that the patient had sustained vertebral fractures secondary to unrecognised nocturnal hypoglycaemic seizures. Intravenous zoledronic acid was administered for secondary fracture prevention. Despite anti-resorptive therapy, the patient sustained a new vertebral fracture after experiencing another hypoglycaemic seizure in his sleep. Bone health in T1DM is complex and not well understood. There are significant challenges in the assessment and management of osteoporosis in T1DM, particularly in young adults, where fracture prediction tools have not been validated. Clinicians should be aware of hypoglycaemia as a significant risk factor for fracture in patients with T1DM.

Learning points:

  • Type 1 diabetes mellitus (T1DM) is a secondary cause of osteoporosis, characterised by reduced bone mass and disturbed bone microarchitecture.

  • Hypoglycaemic seizures generate sufficient compression forces along the thoracic column and can cause fractures in individuals with compromised bone quality.

  • Unrecognised hypoglycaemic seizures should be considered in patients with T1DM presenting with fractures without a history of trauma.

  • Patients with T1DM have increased fracture risk and risk factors should be addressed. Evaluation of bone microarchitecture may provide further insights into mechanisms of fracture in T1DM.

  • Further research is needed to guide the optimal screening and management of bone health in patients with T1DM.

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B Cangiano Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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C Cacciatore Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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L Persani Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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M Bonomi Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

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We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic–pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion.

Learning points:

  • Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.

  • In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.

  • In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.

  • Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.

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