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Open access

Syed Ali Imran, Khaled A Aldahmani, Lynette Penney, Sidney E Croul, David B Clarke, David M Collier, Donato Iacovazzo and Márta Korbonits

Summary

Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy.

Learning points:

  • Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.

  • Unusual, previously not described AIP variant with loss of the stop codon.

  • Phenocopy may occur in families with a disease-causing germline mutation.

Open access

Nikolaos Asonitis, Eva Kassi, Michalis Kokkinos, Ilias Giovanopoulos, Foteini Petychaki and Helen Gogas

Summary

Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.

Learning points:

  • Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.

  • Breast cancer has the highest prevalence of hypercalcemia.

  • The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).

  • In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.

Open access

Irene Berges-Raso, Olga Giménez-Palop, Elisabeth Gabau, Ismael Capel, Assumpta Caixàs and Mercedes Rigla

Summary

Kallmann syndrome is a genetically heterogeneous form of hypogonadotropic hypogonadism caused by gonadotropin-releasing hormone deficiency and characterized by anosmia or hyposmia due to hypoplasia of the olfactory bulbs; osteoporosis and metabolic syndrome can develop due to longstanding untreated hypogonadism. Kallmann syndrome affects 1 in 10 000 men and 1 in 50 000 women. Defects in 17 genes, including KAL1, have been implicated. Kallmann syndrome can be associated with X-linked ichthyosis, a skin disorder characterized by early onset dark, dry, irregular scales affecting the limb and trunk, caused by a defect of the steroid sulfatase gene (STS). Both KAL1 and STS are located in the Xp22.3 region; therefore, deletions in this region cause a contiguous gene syndrome. We report the case of a 32-year-old man with ichthyosis referred for evaluation of excessive height (2.07 m) and weight (BMI: 29.6 kg/m2), microgenitalia and absence of secondary sex characteristics. We diagnosed Kallmann syndrome with ichthyosis due to a deletion in Xp22.3, a rare phenomenon.

Learning points:

  • Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism with anosmia or hyposmia associated with defects in the production or action of gonadotropin-releasing hormone (GnRH) and hypoplasia of the olfactory bulbs.

  • Several genes have been implicated in Kallmann syndrome, including KAL1, located in the Xp22.3 region, which is responsible for X-linked Kallmann syndrome. KAL1 encodes the protein anosmin-1. X-linked ichthyosis is caused by deficiency of the steroid sulfatase enzyme, encoded by STS, which is also located in the Xp22.3 region. Deletions involving this region can affect both genes and result in contiguous gene syndromes.

  • Phenotype can guide clinicians toward suspicion of a specific genetic mutation. KAL1 mutations are mostly related to microgenitalia, unilateral renal agenesis and synkinesia, although patients need not present all these abnormalities.

  • Longstanding untreated hypogonadism is associated with poor sexual health, osteoporosis and metabolic syndrome with the concomitant risk of developing type 2 diabetes mellitus and obesity.

  • Treatment aims to promote the development of secondary sex characteristics, build and sustain normal bone and muscle mass and restore fertility. Treatment can also help minimize some psychological consequences.

  • Treatments available for patients with congenital GnRH deficiency such as Kallmann syndrome include gonadal steroid hormones, human gonadotropins and GnRH. The choice of therapy depends on the goal or goals.

Open access

Dimitrios Haidopoulos, George Bakolas and Lina Michala

Summary

Turner syndrome (TS) has been linked to a number of autoimmune conditions, including lichen sclerosus (LS), at an estimated prevalence of 17%. LS is a known precursor to vulvar cancer. We present a case of vulvar cancer in a 44-year-old woman, who had previously complained of pruritus in the area, a known symptom of LS. Histology confirmed a squamous cell carcinoma with underlying LS. Vulvar assessment for the presence of LS should be undertaken regularly as part of the routine assessments proposed for adult TS women. If LS is identified, then the patient should be warned of the increased risk of vulvar cancer progression and should be monitored closely for signs of the condition.

Learning points

  • Patients with TS are at increased risk of developing LS.

  • LS is a known precursor to vulvar cancer.

  • TS women with LS may be at risk of developing vulvar cancer and should be offered annual vulvar screening and also be aware of signs and symptoms of early vulvar cancer.