Diagnosis and Treatment > Signs and Symptoms > Arthralgia
You are looking at 11 - 15 of 15 items
Search for other papers by Murray B Gordon in
Google Scholar
PubMed
Search for other papers by Kellie L Spiller in
Google Scholar
PubMed
Summary
Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin.
Learning points
-
Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide.
-
Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled.
-
Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.
Search for other papers by Christopher Muir in
Google Scholar
PubMed
Search for other papers by Anthony Dodds in
Google Scholar
PubMed
Garvan Institute of Medical Research, Sydney, Australia
Search for other papers by Katherine Samaras in
Google Scholar
PubMed
Summary
Diamond–Blackfan anaemia (DBA) is a rare cause of bone marrow failure. The incidence of malignancy and endocrine complications are increased in DBA, relative to other inherited bone marrow failure syndromes. We describe an adult woman with DBA who developed osteoporosis and avascular necrosis (AVN) of both distal femora. Such endocrine complications are not uncommon in DBA, but under-appreciated, especially in adulthood. Further, rectal adenocarcinoma was diagnosed at age 32 years, requiring hemi-colectomy and adjuvant chemotherapy. Elevated cancer risk may warrant disease-specific screening guidelines. Genetic predictors of extra-haematopoetic complications in DBA are yet to be established.
Learning points:
-
Endocrine complications are common in DBA.
-
Clinical vigilance is required in managing bone health of DBA patients treated with glucocorticoids.
-
There is currently no reliable way to predict which patients will develop complications of therapy or premature malignancy related to DBA.
-
Complaints of bone or joint pain should prompt screening with targeted magnetic resonance imaging. Osteoporosis screening should be performed routinely.
Search for other papers by Ruth Mangupli in
Google Scholar
PubMed
Search for other papers by Adrian F Daly in
Google Scholar
PubMed
Search for other papers by Elvia Cuauro in
Google Scholar
PubMed
Search for other papers by Paul Camperos in
Google Scholar
PubMed
Search for other papers by Jaime Krivoy in
Google Scholar
PubMed
Search for other papers by Albert Beckers in
Google Scholar
PubMed
Summary
A 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed. Routine hematological, biochemical and hormonal blood tests, including GH and IGF-1 were normal. The clinical picture suggested primary hypertrophic osteoarthropathy (PHOA) rather than acromegaly and radiological studies were supportive of this, demonstrating increased subperiosteal bone formation and increased bone density and cortical thickening. There was widespread joint disease, with narrowing of joint spaces, whereas the knees demonstrated effusions and calcification. A skull X-ray revealed calvarial hyperostosis and a normal sellar outline. Family history was negative. Genetic studies were performed on peripheral blood leukocyte DNA for mutations in the two genes associated with PHOA, 15-hydroxyprostaglandin dehydrogenase (HPGD; OMIM: 601688) and solute carrier organic anion transporter family member 2A1 (SLCO2A1; OMIM: 601460). The sequence of HPGD was normal, whereas the subject was homozygous for a novel pathological variant in SLCO2A1, c.830delT, that predicted a frameshift and early protein truncation (p.Phe277Serfs*8). PHOA, also known as pachydermoperiostosis, is a rare entity caused by abnormal prostaglandin E2 metabolism, and both HPGD and SLCO2A1 are necessary for normal prostaglandin E2 handling. High prostaglandin levels lead to bone formation and resorption and connective tissue inflammation causing arthropathy, in addition to soft tissue swelling.
Learning points:
-
The differential diagnosis of enlarged extremities, coarsened facial features, skin changes and increased sweating in suspected acromegaly is quite limited and primary hypertrophic osteoarthropathy (PHOA) is one of the few conditions that can mimic acromegaly at presentation.
-
PHOA is not associated with abnormalities in GH and IGF-1 secretion and can be readily differentiated from acromegaly by hormonal testing.
-
Clubbing in the setting of diffuse enlargement of joints and extremities in addition to skin changes should alert the physician to the possibility of PHOA, as clubbing is not a usual feature of acromegaly. Underlying causes of secondary hypertrophic osteoarthroapthy (e.g. bronchial neoplasia) should be considered.
-
PHOA is a very rare condition caused by abnormalities in prostaglandin metabolism and has two known genetic causes (HPGD and SLCO2A1 mutations).
-
SLCO2A1 gene mutations lead usually to autosomal recessive PHOA; fewer than 50 SLCO2A1 mutations have been described to date and the current case is only the second in a Hispanic patient.
-
Treatment of primary hypertrophic osteoarthropathy is focused on the management of joint pain usually in the form of non-steroidal anti-inflammatory drug therapy.
Search for other papers by Ekaterina Manuylova in
Google Scholar
PubMed
Search for other papers by Laura M Calvi in
Google Scholar
PubMed
Search for other papers by Catherine Hastings in
Google Scholar
PubMed
Search for other papers by G Edward Vates in
Google Scholar
PubMed
Search for other papers by Mahlon D Johnson in
Google Scholar
PubMed
Search for other papers by William T Cave Jr in
Google Scholar
PubMed
Search for other papers by Ismat Shafiq in
Google Scholar
PubMed
Summary
Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Learning points:
-
Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.
-
The interval between prolactinoma and acromegaly diagnoses can be several decades.
-
Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications.
Search for other papers by Wann Jia Loh in
Google Scholar
PubMed
Search for other papers by Kesavan Sittampalam in
Google Scholar
PubMed
Search for other papers by Suan Cheng Tan in
Google Scholar
PubMed
Search for other papers by Manju Chandran in
Google Scholar
PubMed
Summary
Erdheim–Chester disease (ECD) is a potentially fatal condition characterized by infiltration of multiple organs by non-Langerhans histiocytes. Although endocrine dysfunction has been reported in association with ECD, to date, there have been no previous reports of empty sella syndrome (ESS) associated with it. We report the case of a patient with ECD who had symptomatic ESS. A 55-year-old man of Chinese ethnicity initially presented with symptoms of heart failure, fatigue and knee joint pain. Physical examination revealed xanthelasma, gynaecomastia, lung crepitations, hepatomegaly and diminished testicular volumes. He had laboratory evidence of hypogonadotrophic hypogonadism, secondary hypoadrenalism and GH deficiency. Imaging studies showed diffuse osteosclerosis of the long bones on X-ray, a mass in the right atrium and thickening of the pleura and of the thoracic aorta on fusion positron emission tomography–computed tomography. Magnetic resonance imaging (MRI) of the brain showed an empty sella. The diagnosis of ECD was confirmed by bone biopsy.
Learning points
-
ECD is a multisystemic disease that can affect the pituitary and other organs. The diagnosis of ECD is based on clinical and radiological features and histology, showing lipid-laden CD68+ CD1a− S100− histiocytes surrounded by fibrosis.
-
The finding of xanthelasmas especially in the presence of normal lipid levels in the presence of a multisystem infiltrative disorder should raise the suspicion of ECD.
-
Systemic perturbation of autoimmunity may play a role in the pathogenesis of ECD and is an area that merits further research.