European Journal of Endocrinology (2008) 159 369–373 ISSN 0804-4643 CLINICAL STUDY The pathology of the ulnar nerve in acromegaly Alberto Tagliafico1, Eugenia Resmini2, Raffaella Nizzo3, Lorenzo E Derchi1, Francesco Minuto2, Massimo Giusti2, Carlo Martinoli1 and Diego Ferone2 Departments of 1Radiology ‘R’, DICMI, 2Endocrinological and Medical Sciences (DiSEM) and Center of Excellence for Biomedical Research and 3Neurophysiology, University of Genova, Viale Benedetto XV, 6, I-16132 Genova, Italy (Correspondence should be addressed to D Ferone; Email: [email protected]) Abstract Context: Acromegalic patients may complain of sensory disturbances in their hands. Cubital tunnel syndrome, the ulnar nerve neuropathy at the cubital tunnel (UCT), in acromegalic patients has never been reported. Objective: To describe and assess the prevalence of UCT in acromegalic patients and the effects of 1 year of therapy on UCT. Patients: We examined prospectively 37 acromegalic patients with no history of polyneuropathy, acute trauma at the elbow, no diabetes or hypothyroidism with clinical examination, nerve conduction studies (NCS), and high-resolution ultrasound (US). A control group was made by 50 volunteers. The local ethics committee approved the study and written informed consent was obtained from all subjects involved in the study. Intervention: Clinical history, physical examination, NCS, and US were used to diagnose UCT at the beginning of the study and after 1 year. Results: In 8 of 37 patients, a diagnosis of UCT was made at the beginning of the study reflecting a prevalence of 21%. After 1 year, 5 of 8 (62.5%) patients reported clinical and NCS improvements and evident US reduction of nerve cross-sectional area (CSA; 16.7G2.9 mm2 vs 12.2G3.1 mm2; P!0.001). In 3 of 8 (37.5%) patients, the UCT was unchanged. Ulnar nerve CSA was significantly increased in acromegalic patients with UCT (16.7G2.9 mm2 vs 11.1G2.3 mm2; P!0.047). Conclusion: Ulnar neuropathy could occur in acromegalic patients and can improve in 62% of cases with disease control. Due to the different management and therapeutic approach, it would be important to make differential diagnosis between cubital and carpal tunnel syndrome in acromegaly. European Journal of Endocrinology 159 369–373 Introduction to ulnar nerve entrapment at the elbow which may determine altered sensation in the little and ring fingers Carpal tunnel syndrome (CTS) is a common complication and, in later stages, wasting of the small muscles of the of acromegaly occurring in 20–64% of patients at hand and of the ulnar-side forearm (4). UCT is often diagnosis (1, 2). Sensory disturbances in the hand of misdiagnosed and the adjunct of ultrasound (US) to acromegalic patients may derive from a generalized nerve electrodiagnostic tests increases the sensitivity of the swelling that involves the median nerve and the ulnar diagnosis to 98% (6). Differential diagnosis between CTS nerve (3). Ulnar nerve entrapment at the elbow (cubital and UCT assumes clinical relevance due to the different tunnel syndrome, UCT) is the second most common management and therapeutic approach. Therefore, the peripheral nerve entrapment syndrome following CTS in aim of this study was to assess UCT in acromegalic patients the normal population. UCT is the cause of disability and at the baseline and after 1-year of treatment. pain for patients and, in extreme cases, may progress to loss of function of the hand (4). In the clinical practice, sensory disturbances typically affect acromegalic patients’ hands, but the majorityof investigations deal with median Materials and methods nerve involvement (1–5). In particular, Jenkins et al. elegantly demonstrated by magnetic resonance imaging Patients that the predominate pathologic mechanism of median We prospectively evaluated 37 acromegalic patients (18 neuropathy in acromegaly seems to be edema of the females and 19 males, age range 18–79 years, disease perineural sheathes rather than increased volume of the duration range 1–15 years) and 50 healthy age-, sex-, and carpal tunnel contents (5). However, to the best of our body mass index-matched controls with no history of knowledge, in acromegaly little attention has been given polyneuropathy,acute trauma at the elbow, alcohol abuse, q 2008 European Society of Endocrinology DOI: 10.1530/EJE-08-0327 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 09/27/2021 03:41:38AM via free access 370 A Tagliafico and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159 vitamin B12 deficiency, diabetes or hypothyroidism, with the ulnar nerve with a broadband (17-5 MHz) linear clinical examination, nerve conduction studies (NCS), and array transducer. The adjunct of US to diagnose UCT US to identify the presence of ulnar neuropathy at the increases the sensitivity and specificity of the diagnosis elbow. In these patients, the diagnosis of acromegaly was reaching values of 98% and it is recommended by the based on established criteria (7). At the beginning of the latest developments in neurology (10). US criteria for study, 6 patients had a new diagnosis (de novo) and did not nerve identification were based on anatomical land- receive any previous treatment, 21 previously underwent marks and detection of the fascicular echotexture (11). transsphenoidal neurosurgery (10 of these were also A swollen and hypoechoic ulnar nerve with the loss of treated with somatostatin analogues), 9 underwent the fascicular pattern at the cubital tunnel and a primary medical therapy with somatostatin analogues, narrowing of the nerve as it entered the cubital tunnel and the remaining one underwent radiotherapy and were the US signs of ulnar entrapment at the elbow medical therapy with octreotide. Disease activity was (Fig. 1). Moreover, ulnar nerve cross-sectional area evaluated by growth hormone (GH) measurement during (CSA) was evaluated considering the threshold value for 2 oral glucose tolerance test (OGTT) and the basal value of cubital tunnel syndrome to be an area of 7.5 mm (12). insulin-like growth factor 1 (IGF1), and the patients were Patients with a diagnosis of UCT at the beginning of subdivided into three subgroups according to established the study were reevaluated after 1 year. criteria (7): controlled (nZ17), uncontrolled (nZ12), and partially controlled (nZ8) in whom a discrepancy among Laboratory assays GH during OGTT and basal IGF1 values was noted. The study was approved by the local ethics committee Circulating GH and IGF1 levels were determined as and written informed consent was obtained from all reported previously (13). patients and controls. Statistical analysis Clinical examination Statistical analysis was performed using SPSS 11.0 During physical examination the following in each software (Chicago, Illinois, USA). Mann–Whitney U test patient were systematically assessed: was used for unpaired data to compare patients and 1) Pinprick sensation in the area of the ulnar digital, controls as well as patients’ groups. Wilcoxon signed- palmar cutaneous, and dorsal cutaneous sensory branches; ranks test for related samples was used for comparison of 2) strength of the first dorsal interosseous, abductor digiti the patient with UCT at the beginning of the study and ! minimi, flexor carpi ulnaris,andflexor digitorum profundus after 1 year. P values 0.05 were considered significant. muscles using the Medical Research Council rating scale; and 3) muscle bulk of the hypothenar and first interosseous space (6). Moreover, patients with clinical symptoms of CTS Results according to the American Academy of Neurology (8) were excluded from the follow-up. Clinical examination A total of 37 patients were evaluated. At the beginning of Neurophysiological examination the study, 13 acromegalic patients were asymptomatic Patients identified at physical examination with possible and 15 patients referred sensory disturbances related to UCT underwent NCS to confirm the suspected diagnosis. Motor nerve conduction velocities of the ulnar nerve were calculated from below the elbow to the wrist and along a more than 10 cm segment across the elbow. The median nerve was also evaluated to exclude a Martin– Gruber anastomosis. The diagnosis of ulnar neuropathy at the elbow was made following the criteria of the American Association of Electrodiagnostic Medicine: absolute slow- ing of nerve conduction at the elbow, decreased conduction velocity of more than 10 m/s across the elbow, decreased amplitude of more than 20%, absence of sensory responses, or evidence of muscle atrophy (9). Figure 1 (a) Normal longitudinal 17-5 MHz US of the ulnar nerve at Ultrasonography the cubital tunnel in a normal subject. (b) Evidently enlarged and swollen ulnar nerve in a symptomatic acromegalic patient at the In order to increase the sensitivity of clinical exami- elbow. In this patient, the ulnar nerve CSA on short-axis plane was nation and electrodiagnostic tests (10), we evaluated 27 mm2 (the normal cut-off value is 7.5 mm2). www.eje-online.org Downloaded from Bioscientifica.com at 09/27/2021 03:41:38AM via free access EUROPEAN JOURNAL OF ENDOCRINOLOGY (2008) 159 Cubital tunnel in acromegaly 371 the median nerve, and so these patients were excluded. Concordance with clinical examination, NCS, The remaining nine patients (three de novo, two with and US uncontrolled acromegaly, one partially controlled, and three with controlled acromegaly) complained of sensory Based on the results of these three approaches, we diagnosed UCT in eight patients (Table 1). One patient disturbances (numbness and paresthesias) in the territory with sensory disturbances on the hand as a whole was of distribution of the ulnar nerve. Weakness or atrophy considered as a CTS with a ‘glove’ distribution of in first dorsal interosseous or abductor digiti minimi was paresthesias (14) and was excluded. We considered also noted in one of the nine patients. One of these nine the five patients with normal NCS and abnormal US as symptomatic patients had sensory disturbances in the having UCT because, especially in mild UCT, NCS may hand as a whole and has been excluded because NCS and be normal and US increases the sensitivity of electro- US identified a CTS.