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\begin{document}

\title{Recurrent hypoglycaemia and a slowly rising hemidiaphragm: A case
report.}



\author[1]{Vincent  Simpson}%
\author[1]{Andrew McGovern}%
\affil[1]{Royal Devon and Exeter NHS Foundation Trust}%


\vspace{-1em}



  
  \date{May 23, 2024}


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\selectlanguage{english}
\begin{abstract}
A 92-year-old man presented to the hospital with recurrent hypoglycemia
with a chronically raised right hemidiaphragm. A CT
thorax-abdomen-pelvis showed a large abdominal mass. A `big' IGF-2
secreting non-islet cell tumour was suspected and confirmed. The patient
was treated with low dose prednisolone.%
\end{abstract}%



\sloppy


\textbf{Recurrent hypoglycaemia and a slowly rising hemidiaphragm: A
case report}

A 92-year-old man presented to the hospital with a fall. On arrival of
the ambulance crew at his home he was found to be hypoglycaemic
(1.8mmol/L; reference range 4\selectlanguage{ngerman}·0-6·0 mmol/L) and was treated with
intravenous glucose. He reported several falls over the preceding few
weeks, usually occurring in the morning. He had no other symptoms and no
preceding history of increased hunger or weight change. His past medical
history included chronic obstructive pulmonary disease, ischaemic heart
disease, and chronic lymphocytic leukaemia but not diabetes. He was not
prescribed any glucose-lowering medication. His complete blood count
demonstrated a mild chronic normocytic anaemia (haemoglobin 114g/L;
130-180g/L) but was otherwise unremarkable. Serum electrolytes, liver
function tests, thyroid function tests, and C-reactive protein were all
normal. His chest x-ray showed a chronically raised right hemidiaphragm.
He was kept in overnight for observation and glucose monitoring. At
05:00 he had a further hypoglycaemic episode (venous glucose 1·9
mmol/L). The simultaneous measurement showed an appropriately low
c-peptide (\textless{}94 pmol/L; 370-1470 pmol/L) and low insulin level
(\textless{}2·8 pmol/L; 17·8-173·0 pmol/L)\textbf{.} A short Synacthen
test excluded adrenal insufficiency. An echocardiogram done for a new
ejection systolic murmur showed moderate to severe aortic stenosis but
also showed right atrial compression. We suspected a `big' Insulin-like
growth factor-2 (IGF-2) producing tumour and requested IGF levels and a
CT thorax-abdomen-pelvis. Pending test results, he was started on a
modest dose of hydrocortisone (10mg at night) and an evening snack. His
IGF-1 was at the lower end of the reference range (8·2 nmol/L; 4·6-23·4
nmol/L), with an increased IGF-2:IGF-1 ratio (17·2; \textless{}10
{[}IGF-2 140·7 nmol/L{]}) in keeping with non-islet cell tumour
hypoglycaemia. His CT showed a large heterogeneous mass (18.3 x 15·7cm)
with central calcification above the right hemidiaphragm with associated
partial superior vena cava obstruction and liver displacement
(\textbf{figure 1} ). Retrospectively reviewing his chest x-rays, the
mass was evident as a steadily rising right hemidiaphragm over 10 years
(\textbf{figure 2} ). He experienced no further hypoglycaemia on the low
dose of prednisolone and therefore this was not increased. Due to his
age and comorbidities, this conservative treatment was considered the
optimal treatment option. Subsequent home measurement of his morning
capillary blood glucose levels suggested good prevention of
hypoglycaemic events (ranging 6·1-7·1mmol/L; 4·0-6·0mmol/L).

Non-islet cell tumour hypoglycaemia is a rare cause of hypoglycaemia and
caused by IGF-2 secretion from large tumours usually arising from
mesenchymal origin (41\%), though it can arise from any cell line.1
These tumours produce high molecular weight ``big'' IGF-2 which acts
similarly to insulin, inhibiting glucose release from the liver and
increasing skeletal muscle uptake.2 In turn this suppresses growth
hormone, insulin, IGF-1 and glucagon

release thereby increasing the risk of hypoglycaemia. Treatment is
either with resection of the tumour or, where this is not possible, high
dose steroids (e.g. 30-60mg prednisolone) with either somatostatins or
growth hormone.1,2

This case demonstrates the importance of reviewing serial x-rays for
more insidious slow-growing tumours. Successful suppression of
hypoglycaemic events in non-islet cell tumour hypoglycaemia can be
achieved with relatively low doses of prednisolone (here prednisolone
10mg orally taken at night) although other reports suggest higher doses
are usually needed.1,2

\textbf{Contributors}

VS and AMcG were involved in the clinical care of the patient and the
preparation of the manuscript. Both authors read and approved the final
submitted version. Written informed consent was obtained from the
patient's next of kin as the patient had unfortunately passed away from
unrelated pneumonia at the time of writing.

\textbf{Declaration of interests}

We declare no competing interests.

\textbf{References}

1. De Groot, J. W. B., Rikhof, B., Van Doorn, J., Bilo, H. J. G.,
Alleman, M. A., Honkoop, A. H., \& Van Der Graaf, W. T. A. (2007).
Non-islet cell tumour-induced hypoglycaemia: A review of the literature
including two new cases. \emph{Endocrine-Related Cancer}, \emph{14}(4),
979--993. https://doi.org/10.1677/ERC-07-0161 2. Timothy W. Bodnar,
Maria J. Acevedo, and Massimo Pietropaolo (2013). Management of
Non-Islet-Cell Tumor Hypoglycemia: A Clinical Review.\emph{JCEM},
\emph{99}(3), 713--722.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/CT-TAP-17-04-2020/CT-TAP-17-04-2020}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Case-Report-CXR-Filmstrip-2/Case-Report-CXR-Filmstrip-2}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Case_Report_CXR_Date_Slow.gif`  available at \url{https://authorea.com/users/406188/articles/516944-recurrent-hypoglycaemia-and-a-slowly-rising-hemidiaphragm-a-case-report}

\selectlanguage{english}
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